Pub Date : 2024-03-01DOI: 10.1016/j.jot.2023.12.007
Guoju Hong , Shuqiang Li , Guanqiang Zheng , Xiaoxia Zheng , Qunzhang Zhan , Lin Zhou , Qiushi Wei , Wei He , Zhenqiu Chen
Background/objective
As the pivotal cellular mediators of bone resorption and pathological bone remodeling, osteoclasts have emerged as a prominent target for anti-resorptive interventions. Pinocembrin (PIN), a predominant flavonoid found in damiana, honey, fingerroot, and propolis, has been recognized for its potential therapeutic effects in osteolysis. The purpose of our project is to investigate the potential of PIN to prevent bone resorption in ovariectomized (OVX) mice by suppressing osteoclast production through its underlying mechanisms.
Methods
The study commenced by employing protein-ligand molecular docking to ascertain the specific interaction between PIN and nuclear factor-κB (NF-κB) ligand (RANKL). Subsequently, PIN was introduced to bone marrow macrophages (BMMs) under the stimulation of RANKL. The impact of PIN on osteoclastic activity was assessed through the utilization of a positive TRAcP staining kit and a hydroxyapatite resorption assay. Furthermore, the study investigated the generation of reactive oxygen species (ROS) in osteoclasts induced by RANKL using H2DCFDA. To delve deeper into the underlying mechanisms, molecular cascades triggered by RANKL, including NF-κB, ROS, calcium oscillations, and NFATc1-mediated signaling pathways, were explored using Luciferase gene report, western blot analysis, and quantitative real-time polymerase chain reaction. Moreover, an estrogen-deficient osteoporosis murine model was established to evaluate the therapeutic effects of PIN in vivo.
Results
In this study, we elucidated the profound inhibitory effects of PIN on osteoclastogenesis and bone resorption, achieved through repression of NF-κB and NFATc1-mediated signaling pathways. Notably, PIN also exhibited potent anti-oxidative properties by mitigating RANKL-induced ROS generation and augmenting activities of ROS-scavenging enzymes, ultimately leading to a reduction in intracellular ROS levels. Moreover, PIN effectively abrogated the expression of osteoclast-specific marker genes (Acp5, Cathepsin K, Atp6v0d2, Nfatc1, c-fos, and Mmp9), further underscoring its inhibitory impact on osteoclast differentiation and function. Additionally, employing an in vivo mouse model, we demonstrated that PIN effectively prevented osteoclast-induced bone loss resultant from estrogen deficiency.
Conclusion
Our findings highlight the potent inhibitory effects of PIN on osteoclastogenesis, bone resorption, and RANKL-induced signaling pathways, thereby establishing PIN as a promising therapeutic candidate for the prevention and management of osteolytic bone diseases.
The translational potential of this article
PIN serves as a promising therapeutic agent for the prevention and management of osteolytic bone diseases and holds promise for future clinical applications
{"title":"Therapeutic potential of a prominent dihydroxyflavanone pinocembrin for osteolytic bone disease: In vitro and in vivo evidence","authors":"Guoju Hong , Shuqiang Li , Guanqiang Zheng , Xiaoxia Zheng , Qunzhang Zhan , Lin Zhou , Qiushi Wei , Wei He , Zhenqiu Chen","doi":"10.1016/j.jot.2023.12.007","DOIUrl":"https://doi.org/10.1016/j.jot.2023.12.007","url":null,"abstract":"<div><h3>Background/objective</h3><p>As the pivotal cellular mediators of bone resorption and pathological bone remodeling, osteoclasts have emerged as a prominent target for anti-resorptive interventions. Pinocembrin (PIN), a predominant flavonoid found in damiana, honey, fingerroot, and propolis, has been recognized for its potential therapeutic effects in osteolysis. The purpose of our project is to investigate the potential of PIN to prevent bone resorption in ovariectomized (OVX) mice by suppressing osteoclast production through its underlying mechanisms.</p></div><div><h3>Methods</h3><p>The study commenced by employing protein-ligand molecular docking to ascertain the specific interaction between PIN and nuclear factor-κB (NF-κB) ligand (RANKL). Subsequently, PIN was introduced to bone marrow macrophages (BMMs) under the stimulation of RANKL. The impact of PIN on osteoclastic activity was assessed through the utilization of a positive TRAcP staining kit and a hydroxyapatite resorption assay. Furthermore, the study investigated the generation of reactive oxygen species (ROS) in osteoclasts induced by RANKL using H<sub>2</sub>DCFDA. To delve deeper into the underlying mechanisms, molecular cascades triggered by RANKL, including NF-κB, ROS, calcium oscillations, and NFATc1-mediated signaling pathways, were explored using Luciferase gene report, western blot analysis, and quantitative real-time polymerase chain reaction. Moreover, an estrogen-deficient osteoporosis murine model was established to evaluate the therapeutic effects of PIN <em>in vivo</em>.</p></div><div><h3>Results</h3><p>In this study, we elucidated the profound inhibitory effects of PIN on osteoclastogenesis and bone resorption, achieved through repression of NF-κB and NFATc1-mediated signaling pathways. Notably, PIN also exhibited potent anti-oxidative properties by mitigating RANKL-induced ROS generation and augmenting activities of ROS-scavenging enzymes, ultimately leading to a reduction in intracellular ROS levels. Moreover, PIN effectively abrogated the expression of osteoclast-specific marker genes (<em>Acp5</em>, <em>Cathepsin K</em>, <em>Atp6v0d2</em>, <em>Nfatc1</em>, <em>c-fos</em>, and <em>Mmp9</em>), further underscoring its inhibitory impact on osteoclast differentiation and function. Additionally, employing an <em>in vivo</em> mouse model, we demonstrated that PIN effectively prevented osteoclast-induced bone loss resultant from estrogen deficiency.</p></div><div><h3>Conclusion</h3><p>Our findings highlight the potent inhibitory effects of PIN on osteoclastogenesis, bone resorption, and RANKL-induced signaling pathways, thereby establishing PIN as a promising therapeutic candidate for the prevention and management of osteolytic bone diseases.</p></div><div><h3>The translational potential of this article</h3><p>PIN serves as a promising therapeutic agent for the prevention and management of osteolytic bone diseases and holds promise for future clinical applications","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214031X24000032/pdfft?md5=15f83d17c1291d711859426a686e54bd&pid=1-s2.0-S2214031X24000032-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140297005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-01DOI: 10.1016/j.jot.2023.10.003
Tianshu Jiang , Sing-Hin Lau , Jiang Zhang , Lok-Chun Chan , Wei Wang , Ping-Keung Chan , Jing Cai , Chunyi Wen
Osteoarthritis (OA) is one of the fast-growing disability-related diseases worldwide, which has significantly affected the quality of patients' lives and brings about substantial socioeconomic burdens in medical expenditure. There is currently no cure for OA once the bone damage is established. Unfortunately, the existing radiological examination is limited to grading the disease's severity and is insufficient to precisely diagnose OA, detect early OA or predict OA progression. Therefore, there is a pressing need to develop novel approaches in medical image analysis to detect subtle changes for identifying early OA development and rapid progressors. Recently, radiomics has emerged as a unique approach to extracting high-dimensional imaging features that quantitatively characterise visible or hidden information from routine medical images. Radiomics data mining via machine learning has empowered precise diagnoses and prognoses of disease, mainly in oncology. Mounting evidence has shown its great potential in aiding the diagnosis and contributing to the study of musculoskeletal diseases. This paper will summarise the current development of radiomics at the crossroads between engineering and medicine and discuss the application and perspectives of radiomics analysis for OA diagnosis and prognosis.
The translational potential of this article
Radiomics is a novel approach used in oncology, and it may also play an essential role in the diagnosis and prognosis of OA. By transforming medical images from qualitative interpretation to quantitative data, radiomics could be the solution for precise early OA detection, progression tracking, and treatment efficacy prediction. Since the application of radiomics in OA is still in the early stages and primarily focuses on fundamental studies, this review may inspire more explorations and bring more promising diagnoses, prognoses, and management results of OA.
骨关节炎（OA）是全球快速增长的残疾相关疾病之一，严重影响了患者的生活质量，并在医疗支出方面带来了巨大的社会经济负担。目前，骨损伤一旦形成，就无法治愈。遗憾的是，现有的放射学检查仅限于对疾病的严重程度进行分级，不足以精确诊断 OA、检测早期 OA 或预测 OA 的进展。因此，亟需开发新的医学图像分析方法来检测细微变化，以识别早期 OA 的发展和快速进展者。最近，放射组学作为一种独特的方法出现了，它能从常规医学图像中提取高维成像特征，定量描述可见或隐藏信息。通过机器学习进行的放射组学数据挖掘有助于疾病的精确诊断和预后，主要是在肿瘤学领域。越来越多的证据表明，放射组学在辅助诊断和促进肌肉骨骼疾病研究方面具有巨大潜力。本文将总结放射组学在工程与医学交叉领域的发展现状，并探讨放射组学分析在 OA 诊断和预后方面的应用和前景。通过将医学影像从定性解读转化为定量数据，放射组学可以成为早期OA精确检测、进展跟踪和疗效预测的解决方案。由于放射组学在 OA 中的应用仍处于早期阶段，且主要集中于基础研究，本综述可能会激发更多的探索，为 OA 的诊断、预后和管理带来更多希望。
{"title":"Radiomics signature of osteoarthritis: Current status and perspective","authors":"Tianshu Jiang , Sing-Hin Lau , Jiang Zhang , Lok-Chun Chan , Wei Wang , Ping-Keung Chan , Jing Cai , Chunyi Wen","doi":"10.1016/j.jot.2023.10.003","DOIUrl":"https://doi.org/10.1016/j.jot.2023.10.003","url":null,"abstract":"<div><p>Osteoarthritis (OA) is one of the fast-growing disability-related diseases worldwide, which has significantly affected the quality of patients' lives and brings about substantial socioeconomic burdens in medical expenditure. There is currently no cure for OA once the bone damage is established. Unfortunately, the existing radiological examination is limited to grading the disease's severity and is insufficient to precisely diagnose OA, detect early OA or predict OA progression. Therefore, there is a pressing need to develop novel approaches in medical image analysis to detect subtle changes for identifying early OA development and rapid progressors. Recently, radiomics has emerged as a unique approach to extracting high-dimensional imaging features that quantitatively characterise visible or hidden information from routine medical images. Radiomics data mining via machine learning has empowered precise diagnoses and prognoses of disease, mainly in oncology. Mounting evidence has shown its great potential in aiding the diagnosis and contributing to the study of musculoskeletal diseases. This paper will summarise the current development of radiomics at the crossroads between engineering and medicine and discuss the application and perspectives of radiomics analysis for OA diagnosis and prognosis.</p></div><div><h3>The translational potential of this article</h3><p>Radiomics is a novel approach used in oncology, and it may also play an essential role in the diagnosis and prognosis of OA. By transforming medical images from qualitative interpretation to quantitative data, radiomics could be the solution for precise early OA detection, progression tracking, and treatment efficacy prediction. Since the application of radiomics in OA is still in the early stages and primarily focuses on fundamental studies, this review may inspire more explorations and bring more promising diagnoses, prognoses, and management results of OA.</p></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214031X23000773/pdfft?md5=b50ff211add5182c066ae52dfc5ceaf2&pid=1-s2.0-S2214031X23000773-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140139030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-01DOI: 10.1016/j.jot.2024.02.008
Lixia Huang , Zhidao Xia , Derick Wade , Jicai Liu , Guoyong Zhou , Chuanhua Yu , Helen Dawes , Patrick Esser , Shijun Wei , Jiuhong Song
Background
Exercise is recommended as the first-line management for knee osteoarthritis (KOA); however, it is difficult to determine which specific exercises are more effective. This study aimed to explore the potential mechanism and effectiveness of a leg-swinging exercise practiced in China, called ‘KOA pendulum therapy’ (KOAPT). Intraarticular hydrostatic and dynamic pressure (IHDP) are suggested to partially explain the signs and symptoms of KOA. As such this paper set out to explore this mechanism in vivo in minipigs and in human volunteers alongside a feasibility clinical trial. The objective of this study is 1) to analyze the effect of KOAPT on local mechanical and circulation environment of the knee in experimental animals and healthy volunteers; and 2) to test if it is feasible to run a large sample, randomized/single blind clinical trial.
Methods
IHDP of the knee was measured in ten minipigs and ten volunteers (five healthy and five KOA patients). The effect of leg swinging on synovial blood flow and synovial fluid content depletion in minipigs were also measured. Fifty KOA patients were randomly divided into two groups for a feasibility clinical trial. One group performed KOAPT (targeting 1000 swings/leg/day), and the other performed walking exercise (targeting 4000 steps/day) for 12 weeks with 12 weeks of follow-up.
Results
The results showed dynamic intra-articular pressure changes in the knee joint, increases in local blood flow, and depletion of synovial fluid contents during pendulum leg swinging in minipigs. The intra-articular pressure in healthy human knee joints was −11.32 ± 0.21 (cmH2O), whereas in KOA patients, it was −3.52 ± 0.34 (cmH2O). Measures were completed by 100% of participants in all groups with 95–98% adherence to training in both groups in the feasibility clinical trial. There were significant decreases in the Oxford knee score in both KOAPT and walking groups after intervention (p < 0.01), but no significant differences between the two groups.
Conclusion
We conclude that KOAPT exhibited potential as an intervention to improve symptoms of KOA possibly through a mechanism of normalising mechanical pressure in the knee; however, optimisation of the method, longer-term intervention and a large sample randomized-single blind clinical trial with a minimal 524 cases are needed to demonstrate whether there is any superior benefit over other exercises.
The translational potential of this article
The research aimed to investigate the effect of an ancient leg-swinging exercise on knee osteoarthritis. A minipig animal model was used to establish the potential mechanism underlying the exercise of knee osteoarthritis pendulum therapy, followed by a randomised, single-blind feasibility clinical trial in comparison with a commonly-practised walking exercise regimen. Based
{"title":"Knee osteoarthritis pendulum therapy: In vivo evaluation and a randomised, single-blind feasibility clinical trial","authors":"Lixia Huang , Zhidao Xia , Derick Wade , Jicai Liu , Guoyong Zhou , Chuanhua Yu , Helen Dawes , Patrick Esser , Shijun Wei , Jiuhong Song","doi":"10.1016/j.jot.2024.02.008","DOIUrl":"https://doi.org/10.1016/j.jot.2024.02.008","url":null,"abstract":"<div><h3>Background</h3><p>Exercise is recommended as the first-line management for knee osteoarthritis (KOA); however, it is difficult to determine which specific exercises are more effective. This study aimed to explore the potential mechanism and effectiveness of a leg-swinging exercise practiced in China, called ‘KOA pendulum therapy’ (KOAPT). Intraarticular hydrostatic and dynamic pressure (IHDP) are suggested to partially explain the signs and symptoms of KOA. As such this paper set out to explore this mechanism <em>in vivo</em> in minipigs and in human volunteers alongside a feasibility clinical trial. The objective of this study is 1) to analyze the effect of KOAPT on local mechanical and circulation environment of the knee in experimental animals and healthy volunteers; and 2) to test if it is feasible to run a large sample, randomized/single blind clinical trial.</p></div><div><h3>Methods</h3><p>IHDP of the knee was measured in ten minipigs and ten volunteers (five healthy and five KOA patients). The effect of leg swinging on synovial blood flow and synovial fluid content depletion in minipigs were also measured. Fifty KOA patients were randomly divided into two groups for a feasibility clinical trial. One group performed KOAPT (targeting 1000 swings/leg/day), and the other performed walking exercise (targeting 4000 steps/day) for 12 weeks with 12 weeks of follow-up.</p></div><div><h3>Results</h3><p>The results showed dynamic intra-articular pressure changes in the knee joint, increases in local blood flow, and depletion of synovial fluid contents during pendulum leg swinging in minipigs. The intra-articular pressure in healthy human knee joints was −11.32 ± 0.21 (cmH<sub>2</sub>O), whereas in KOA patients, it was −3.52 ± 0.34 (cmH<sub>2</sub>O). Measures were completed by 100% of participants in all groups with 95–98% adherence to training in both groups in the feasibility clinical trial. There were significant decreases in the Oxford knee score in both KOAPT and walking groups after intervention (<em>p</em> < 0.01), but no significant differences between the two groups.</p></div><div><h3>Conclusion</h3><p>We conclude that KOAPT exhibited potential as an intervention to improve symptoms of KOA possibly through a mechanism of normalising mechanical pressure in the knee; however, optimisation of the method, longer-term intervention and a large sample randomized-single blind clinical trial with a minimal 524 cases are needed to demonstrate whether there is any superior benefit over other exercises.</p></div><div><h3>The translational potential of this article</h3><p>The research aimed to investigate the effect of an ancient leg-swinging exercise on knee osteoarthritis. A minipig animal model was used to establish the potential mechanism underlying the exercise of knee osteoarthritis pendulum therapy, followed by a randomised, single-blind feasibility clinical trial in comparison with a commonly-practised walking exercise regimen. Based","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214031X2400024X/pdfft?md5=756529d2e2dd68724248a110da60a8e2&pid=1-s2.0-S2214031X2400024X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140535949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-01DOI: 10.1016/j.jot.2023.12.004
Zhihong Xu , Senlin Chai , Dongyang Chen , Weijun Wang , Jin Dai , Xiaofeng Zhang , Jianghui Qin , Kai Song , Xinhua Li , Jing Han , Qing Chang , Miaofeng Zhang , Chenxi Xue , Jun Lu , Lidong Wu , Yunfeng Yao , Lan Li , Qing Jiang
Objective
To evaluate the accuracy and safety of the LANCET robotic system, a robot arm assisted operation system for total hip arthroplasty via a multicenter clinical randomized controlled trial.
Methods
A total of 116 patients were randomized into two groups: LANCET robotic arm assisted THA group (N = 58) and the conventional THA group (N = 58). General information about the patients was collected preoperatively. Operational time and bleeding were recorded during the surgery. The position of the acetabular prosthesis was evaluated by radiographs one week after surgery and compared with preoperative planning. Harris score, hip mobility, prosthesis position and angle and complications were compared between the two groups at three months postoperatively.
Results
None of the 111 patients who ultimately completed the 3-month follow-up experienced adverse events such as hip dislocation and infection during follow-up. In the RAA group, 52 (92.9 %) patients were located in the Lewinnek safe zone and 49 (87.5 %) patients were located in the Callanan safe zone. In the control group were 47 (85.5 %) and 44 (80.0 %) patients, respectively. In the RAA group, 53 (94.6 %) patients had a postoperative acetabular inclination angle and 51 (91.1 %) patients had an acetabular version angle within a deviation of 5° from the preoperative plan. These numbers were significantly higher than those of the control group, which consisted of 42 (76.4 %) and 34 (61.8 %) patients respectively. There were no significant differences between the two groups of subjects in terms of general condition, intraoperative bleeding, hip mobility, and adverse complications.
Conclusion
The results of this prospective randomized, multicenter, parallel-controlled clinical study demonstrated that the LANCET robotic system leads conventional THA surgery in accuracy of acetabular cup placement and does not differ from conventional THA surgery in terms of postoperative hip functional recovery and complications.
The translational potential of this article
In the past, the success rate of total hip arthroplasty (THA) relied heavily on the surgeon's experience. As a result, junior doctors needed extensive training to become proficient in this technique. However, the introduction of surgical robots has significantly improved this situation. By utilizing robotic assistance, both junior and senior doctors can perform THA quickly and efficiently. This advancement is crucial for the widespread adoption of THA, as patients can now receive surgical treatment in local facilities instead of overwhelming larger hospitals and straining medical resources. Moreover, the development of surgical robots with fully independent intellectual property rights holds immense value in overcoming the limitations of high-end medical equipment. This aligns with the objectives outlined in the 14th Five Year Plan
{"title":"The LANCET robotic system can improve surgical efficiency in total hip arthroplasty: A prospective randomized, multicenter, parallel-controlled clinical trial","authors":"Zhihong Xu , Senlin Chai , Dongyang Chen , Weijun Wang , Jin Dai , Xiaofeng Zhang , Jianghui Qin , Kai Song , Xinhua Li , Jing Han , Qing Chang , Miaofeng Zhang , Chenxi Xue , Jun Lu , Lidong Wu , Yunfeng Yao , Lan Li , Qing Jiang","doi":"10.1016/j.jot.2023.12.004","DOIUrl":"https://doi.org/10.1016/j.jot.2023.12.004","url":null,"abstract":"<div><h3>Objective</h3><p>To evaluate the accuracy and safety of the LANCET robotic system, a robot arm assisted operation system for total hip arthroplasty via a multicenter clinical randomized controlled trial.</p></div><div><h3>Methods</h3><p>A total of 116 patients were randomized into two groups: LANCET robotic arm assisted THA group (N = 58) and the conventional THA group (N = 58). General information about the patients was collected preoperatively. Operational time and bleeding were recorded during the surgery. The position of the acetabular prosthesis was evaluated by radiographs one week after surgery and compared with preoperative planning. Harris score, hip mobility, prosthesis position and angle and complications were compared between the two groups at three months postoperatively.</p></div><div><h3>Results</h3><p>None of the 111 patients who ultimately completed the 3-month follow-up experienced adverse events such as hip dislocation and infection during follow-up. In the RAA group, 52 (92.9 %) patients were located in the Lewinnek safe zone and 49 (87.5 %) patients were located in the Callanan safe zone. In the control group were 47 (85.5 %) and 44 (80.0 %) patients, respectively. In the RAA group, 53 (94.6 %) patients had a postoperative acetabular inclination angle and 51 (91.1 %) patients had an acetabular version angle within a deviation of 5° from the preoperative plan. These numbers were significantly higher than those of the control group, which consisted of 42 (76.4 %) and 34 (61.8 %) patients respectively. There were no significant differences between the two groups of subjects in terms of general condition, intraoperative bleeding, hip mobility, and adverse complications.</p></div><div><h3>Conclusion</h3><p>The results of this prospective randomized, multicenter, parallel-controlled clinical study demonstrated that the LANCET robotic system leads conventional THA surgery in accuracy of acetabular cup placement and does not differ from conventional THA surgery in terms of postoperative hip functional recovery and complications.</p></div><div><h3>The translational potential of this article</h3><p>In the past, the success rate of total hip arthroplasty (THA) relied heavily on the surgeon's experience. As a result, junior doctors needed extensive training to become proficient in this technique. However, the introduction of surgical robots has significantly improved this situation. By utilizing robotic assistance, both junior and senior doctors can perform THA quickly and efficiently. This advancement is crucial for the widespread adoption of THA, as patients can now receive surgical treatment in local facilities instead of overwhelming larger hospitals and straining medical resources. Moreover, the development of surgical robots with fully independent intellectual property rights holds immense value in overcoming the limitations of high-end medical equipment. This aligns with the objectives outlined in the 14th Five Year Plan ","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214031X23001055/pdfft?md5=f44c0da63c19ab54ffac6cdb70ec2524&pid=1-s2.0-S2214031X23001055-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140348067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-01DOI: 10.1016/j.jot.2023.12.001
Xiaoyu Li , Lei Hu , Xue Wang , Huan Liu , Chunmei Zhang , Jinsong Wang , Xiaogang Wang , Songlin Wang
Background
Nitrate, a key component of saliva, has been shown widely physiological functions in the human body. But its function on bone metabolism remains unclear. The aim of this study was to investigate the function and mechanism of saliva nitrate on osteoporosis and the function of bone marrow mesenchymal stem cells (BMSCs).
Methods
Saliva nitrate removal or supplemental interventions were performed for 1 month in ovariectomized (OVX) osteopenia mice. The nitrate levels in saliva and serum were detected. The bone formation and bone microarchitecture in the OVX mouse model were investigated by quantitative Micro--computed tomography imaging, histological staining and serum bone biomarker analysis. The effects of nitrate on the functional homeostasis of BMSCs in OVX mice were explored by Ki67 immunofluorescence staining, Ki67 flow staining, alizarin red staining, qPCR and western blotting. Finally, downstream signaling pathways were screened by proteomics and verified by western blotting.
Results
The results showed that nitrate deficiency exacerbated osteoporosis, while nitrate administration prevent osteoporosis in OVX mice. Nitrate increased the expression of PINP, a biomarker of bone formation, in OVX mice. Besides, nitrate enhanced the proliferative capacity and osteogenic function of BMSCs in OVX mice in vitro and in vivo. In addition, nitrate upregulated the expression levels of osteogenesis-related genes ALP, Run2 and OPN of BMSCs. EGFR and mTOR signaling were screened as the key downstream of nitrate, and phosphorylated protein levels of its subfamily members AKT, ERK and S6K were significantly upregulated by nitrate.
Conclusion
The present results showed saliva nitrate preventively protects against osteoporosis through enhances the proliferation and osteogenic differentiation potential of BMSCs. The effects of nitrate on bone homeostasis are closely related to the EGFR/AKT/ERK and mTOR/S6K signaling axes.
The translational potential of this article
Our study provides experimental evidence for the use of saliva nitrate as an effective candidate for the prevention of osteoporosis and maintenance of bone homeostasis.
{"title":"Salivary nitrate prevents osteoporosis via regulating bone marrow mesenchymal stem cells proliferation and differentiation","authors":"Xiaoyu Li , Lei Hu , Xue Wang , Huan Liu , Chunmei Zhang , Jinsong Wang , Xiaogang Wang , Songlin Wang","doi":"10.1016/j.jot.2023.12.001","DOIUrl":"https://doi.org/10.1016/j.jot.2023.12.001","url":null,"abstract":"<div><h3>Background</h3><p>Nitrate, a key component of saliva, has been shown widely physiological functions in the human body. But its function on bone metabolism remains unclear. The aim of this study was to investigate the function and mechanism of saliva nitrate on osteoporosis and the function of bone marrow mesenchymal stem cells (BMSCs).</p></div><div><h3>Methods</h3><p>Saliva nitrate removal or supplemental interventions were performed for 1 month in ovariectomized (OVX) osteopenia mice. The nitrate levels in saliva and serum were detected. The bone formation and bone microarchitecture in the OVX mouse model were investigated by quantitative Micro--computed tomography imaging, histological staining and serum bone biomarker analysis. The effects of nitrate on the functional homeostasis of BMSCs in OVX mice were explored by Ki67 immunofluorescence staining, Ki67 flow staining, alizarin red staining, qPCR and western blotting. Finally, downstream signaling pathways were screened by proteomics and verified by western blotting.</p></div><div><h3>Results</h3><p>The results showed that nitrate deficiency exacerbated osteoporosis, while nitrate administration prevent osteoporosis in OVX mice. Nitrate increased the expression of PINP, a biomarker of bone formation, in OVX mice. Besides, nitrate enhanced the proliferative capacity and osteogenic function of BMSCs in OVX mice <em>in vitro</em> and <em>in vivo</em>. In addition, nitrate upregulated the expression levels of osteogenesis-related genes <em>ALP</em>, <em>Run2</em> and <em>OPN</em> of BMSCs. EGFR and mTOR signaling were screened as the key downstream of nitrate, and phosphorylated protein levels of its subfamily members AKT, ERK and S6K were significantly upregulated by nitrate.</p></div><div><h3>Conclusion</h3><p>The present results showed saliva nitrate preventively protects against osteoporosis through enhances the proliferation and osteogenic differentiation potential of BMSCs. The effects of nitrate on bone homeostasis are closely related to the EGFR/AKT/ERK and mTOR/S6K signaling axes.</p></div><div><h3>The translational potential of this article</h3><p>Our study provides experimental evidence for the use of saliva nitrate as an effective candidate for the prevention of osteoporosis and maintenance of bone homeostasis.</p></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214031X2300102X/pdfft?md5=ee55e511ac1e2de6eb40aa24e12ede40&pid=1-s2.0-S2214031X2300102X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140209274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-01DOI: 10.1016/j.jot.2024.02.003
Yang Liu, Yiming Dou, Xun Sun, Qiang Yang
As a permanent state of cell cycle arrest, cellular senescence has become an important factor in aging and age-related diseases. As a central regulator of physiology and pathology associated with cellular senescence, the senescence associated secretory phenotype can create an inflammatory and catabolic environment through autocrine and paracrine ways, ultimately affecting tissue microstructure. As an age-related disease, the correlation between intervertebral disc degeneration and cellular senescence has been confirmed by many studies. Various pathological factors in the microenvironment of intervertebral disc degeneration promote senescent cells to produce and accumulate and express excessive senescence associated secretory phenotype. In this case, senescence associated secretory phenotype has received considerable attention as a potential target for delaying or treating disc degeneration. Therefore, we reviewed the latest research progress of senescence associated secretory phenotype, related regulatory mechanisms and intervertebral disc cell senescence treatment strategies. It is expected that further understanding of the underlying mechanism between cellular senescence pathology and intervertebral disc degeneration will help to formulate reasonable senescence regulation strategies, so as to achieve ideal therapeutic effects.
The translational potential of this article
Existing treatment strategies often fall short in addressing the challenge of repairing intervertebral disc Intervertebral disc degeneration（IVD） degeneration. The accumulation of senescent cells and the continuous release of senescence-associated secretory phenotype (SASP) perpetually impede disc homeostasis and hinder tissue regeneration. This impairment in repair capability presents a significant obstacle to the practical clinical implementation of strategies for intervertebral disc degeneration. As a result, we present a comprehensive overview of the latest advancements in research, the associated regulatory mechanisms, and strategies for treating SASP in IVD cells. This article aims to investigate effective interventions for delaying the onset and progression of age-related intervertebral disc degeneration. In an era where the aging population is becoming increasingly prominent, this endeavor holds paramount practical and translational significance.
{"title":"Mechanisms and therapeutic strategies for senescence-associated secretory phenotype in the intervertebral disc degeneration microenvironment","authors":"Yang Liu, Yiming Dou, Xun Sun, Qiang Yang","doi":"10.1016/j.jot.2024.02.003","DOIUrl":"https://doi.org/10.1016/j.jot.2024.02.003","url":null,"abstract":"<div><p>As a permanent state of cell cycle arrest, cellular senescence has become an important factor in aging and age-related diseases. As a central regulator of physiology and pathology associated with cellular senescence, the senescence associated secretory phenotype can create an inflammatory and catabolic environment through autocrine and paracrine ways, ultimately affecting tissue microstructure. As an age-related disease, the correlation between intervertebral disc degeneration and cellular senescence has been confirmed by many studies. Various pathological factors in the microenvironment of intervertebral disc degeneration promote senescent cells to produce and accumulate and express excessive senescence associated secretory phenotype. In this case, senescence associated secretory phenotype has received considerable attention as a potential target for delaying or treating disc degeneration. Therefore, we reviewed the latest research progress of senescence associated secretory phenotype, related regulatory mechanisms and intervertebral disc cell senescence treatment strategies. It is expected that further understanding of the underlying mechanism between cellular senescence pathology and intervertebral disc degeneration will help to formulate reasonable senescence regulation strategies, so as to achieve ideal therapeutic effects.</p></div><div><h3>The translational potential of this article</h3><p>Existing treatment strategies often fall short in addressing the challenge of repairing intervertebral disc Intervertebral disc degeneration（IVD） degeneration. The accumulation of senescent cells and the continuous release of senescence-associated secretory phenotype (SASP) perpetually impede disc homeostasis and hinder tissue regeneration. This impairment in repair capability presents a significant obstacle to the practical clinical implementation of strategies for intervertebral disc degeneration. As a result, we present a comprehensive overview of the latest advancements in research, the associated regulatory mechanisms, and strategies for treating SASP in IVD cells. This article aims to investigate effective interventions for delaying the onset and progression of age-related intervertebral disc degeneration. In an era where the aging population is becoming increasingly prominent, this endeavor holds paramount practical and translational significance.</p></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214031X24000172/pdfft?md5=e6c45484a898ce16b831da4e835bf416&pid=1-s2.0-S2214031X24000172-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140104138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-01DOI: 10.1016/j.jot.2024.01.002
Dong Wang , Yujun Zhang , Liangping Zhang , Du He , Lan Zhao , Zhimin Miao , Wei Cheng , Chengyue Zhu , Li Zhu , Wei Zhang , Hongting Jin , Hang Zhu , Hao Pan
Background
Osteoarthritis (OA) is a degenerative joint disease characterized by the breakdown of joint cartilage and underlying bone. Macrophages are a type of white blood cell that plays a critical role in the immune system and can be found in various tissues, including joints. Research on the relationship between OA and macrophages is essential to understand the mechanisms underlying the development and progression of OA.
Objective
This study was performed to analyze the functions of the IRF1-GCN5-SETD2-SMARCC1 axis in osteoarthritis (OA) development.
Methods
A single-cell RNA sequencing (scRNA-seq) dataset, was subjected to a comprehensive analysis aiming to identify potential regulators implicated in the progression of osteoarthritis (OA). In order to investigate the role of IRF1 and SMARCC1, knockdown experiments were conducted in both OA-induced rats and interleukin (IL)-1β-stimulated chondrocytes, followed by the assessment of OA-like symptoms, secretion of inflammatory cytokines, and polarization of macrophages. Furthermore, the study delved into the identification of aberrant epigenetic modifications and functional enzymes responsible for the regulation of SMARCC1 by IRF1. To evaluate the clinical significance of the factors under scrutiny, a cohort comprising 13 patients diagnosed with OA and 7 fracture patients without OA was included in the analysis.
Results
IRF1 was found to exert regulatory control over the expression of SMARCC1, thus playing a significant role in the development of osteoarthritis (OA). The knockdown of either IRF1 or SMARCC1 disrupted the pro-inflammatory effects induced by IL-1β in chondrocytes, leading to a mitigation of OA-like symptoms, including inflammatory infiltration, cartilage degradation, and tissue injury, in rat models. Additionally, this intervention resulted in a reduction in the predominance of M1 macrophages both in vitro and in vivo. Significant epigenetic modifications, such as abundant H3K27ac and H3K4me3 marks, were observed near the SMARCC1 promoter and 10 kb upstream region. These modifications were attributed to the recruitment of GCN5 and SETD2, which are functional enzymes responsible for these modifications. Remarkably, the overexpression of either GCN5 or SETD2 restored SMARCC1 expression in rat cartilages or chondrocytes, consequently exacerbating the OA-like symptoms.
Conclusion
This research postulates that the transcriptional activity of SMARCC1 can be influenced by IRF1 through the recruitment of GCN5 and SETD2, consequently regulating the H3K27ac and H3K4me3 modifications in close proximity to the SMARCC1 promoter and 10 kb upstream region. These modifications, in turn, facilitate the M1 skewing of macrophages and contribute to the progression of osteoarthritis (OA).
The Translational Potential of this Article
The study demonstrated that the r
背景骨关节炎（OA）是一种退行性关节疾病，其特点是关节软骨和下层骨质破坏。巨噬细胞是一种白细胞，在免疫系统中发挥着关键作用，可在包括关节在内的各种组织中发现。本研究旨在分析IRF1-GCN5-SETD2-SMARCC1轴在骨关节炎（OA）发展过程中的功能。方法对单细胞RNA测序（scRNA-seq）数据集进行综合分析，旨在确定与骨关节炎（OA）进展有关的潜在调控因子。为了研究 IRF1 和 SMARCC1 的作用，研究人员在 OA 诱导的大鼠和白细胞介素（IL）-1β 刺激的软骨细胞中进行了基因敲除实验，随后评估了 OA 样症状、炎症细胞因子的分泌和巨噬细胞的极化。此外，该研究还深入研究了IRF1调控SMARCC1的异常表观遗传修饰和功能酶。结果发现IRF1对SMARCC1的表达起着调控作用，因此在骨关节炎（OA）的发生发展中起着重要作用。在大鼠模型中，敲除 IRF1 或 SMARCC1 会破坏 IL-1β 在软骨细胞中诱导的促炎效应，从而减轻 OA 类症状，包括炎症浸润、软骨退化和组织损伤。此外，这种干预还能减少体外和体内 M1 巨噬细胞的数量。在SMARCC1启动子和10 kb上游区域附近观察到了显著的表观遗传修饰，如大量的H3K27ac和H3K4me3标记。这些修饰归因于 GCN5 和 SETD2 的招募，它们是负责这些修饰的功能酶。值得注意的是，过量表达 GCN5 或 SETD2 可恢复 SMARCC1 在大鼠软骨或软骨细胞中的表达，从而加重 OA 样症状。这些修饰反过来又促进了巨噬细胞的M1倾斜，并导致骨关节炎（OA）的发展。敲除IRF1或SMARCC1会破坏IL-1β在软骨细胞中诱导的促炎效应，从而减轻大鼠模型中的OA样症状。这些症状包括炎症浸润、软骨退化和组织损伤。这些研究结果表明，以IRF1-SMARCC1调控轴以及相关的表观遗传修饰为靶点，有可能成为开发OA疗法的一种新方法，为疾病管理和改善患者预后提供新的机会。
{"title":"IRF1 governs the expression of SMARCC1 via the GCN5-SETD2 axis and actively engages in the advancement of osteoarthritis","authors":"Dong Wang , Yujun Zhang , Liangping Zhang , Du He , Lan Zhao , Zhimin Miao , Wei Cheng , Chengyue Zhu , Li Zhu , Wei Zhang , Hongting Jin , Hang Zhu , Hao Pan","doi":"10.1016/j.jot.2024.01.002","DOIUrl":"https://doi.org/10.1016/j.jot.2024.01.002","url":null,"abstract":"<div><h3>Background</h3><p>Osteoarthritis (OA) is a degenerative joint disease characterized by the breakdown of joint cartilage and underlying bone. Macrophages are a type of white blood cell that plays a critical role in the immune system and can be found in various tissues, including joints. Research on the relationship between OA and macrophages is essential to understand the mechanisms underlying the development and progression of OA.</p></div><div><h3>Objective</h3><p>This study was performed to analyze the functions of the IRF1-GCN5-SETD2-SMARCC1 axis in osteoarthritis (OA) development.</p></div><div><h3>Methods</h3><p>A single-cell RNA sequencing (scRNA-seq) dataset, was subjected to a comprehensive analysis aiming to identify potential regulators implicated in the progression of osteoarthritis (OA). In order to investigate the role of IRF1 and SMARCC1, knockdown experiments were conducted in both OA-induced rats and interleukin (IL)-1β-stimulated chondrocytes, followed by the assessment of OA-like symptoms, secretion of inflammatory cytokines, and polarization of macrophages. Furthermore, the study delved into the identification of aberrant epigenetic modifications and functional enzymes responsible for the regulation of SMARCC1 by IRF1. To evaluate the clinical significance of the factors under scrutiny, a cohort comprising 13 patients diagnosed with OA and 7 fracture patients without OA was included in the analysis.</p></div><div><h3>Results</h3><p>IRF1 was found to exert regulatory control over the expression of SMARCC1, thus playing a significant role in the development of osteoarthritis (OA). The knockdown of either IRF1 or SMARCC1 disrupted the pro-inflammatory effects induced by IL-1β in chondrocytes, leading to a mitigation of OA-like symptoms, including inflammatory infiltration, cartilage degradation, and tissue injury, in rat models. Additionally, this intervention resulted in a reduction in the predominance of M1 macrophages both in vitro and in vivo. Significant epigenetic modifications, such as abundant H3K27ac and H3K4me3 marks, were observed near the SMARCC1 promoter and 10 kb upstream region. These modifications were attributed to the recruitment of GCN5 and SETD2, which are functional enzymes responsible for these modifications. Remarkably, the overexpression of either GCN5 or SETD2 restored SMARCC1 expression in rat cartilages or chondrocytes, consequently exacerbating the OA-like symptoms.</p></div><div><h3>Conclusion</h3><p>This research postulates that the transcriptional activity of SMARCC1 can be influenced by IRF1 through the recruitment of GCN5 and SETD2, consequently regulating the H3K27ac and H3K4me3 modifications in close proximity to the SMARCC1 promoter and 10 kb upstream region. These modifications, in turn, facilitate the M1 skewing of macrophages and contribute to the progression of osteoarthritis (OA).</p></div><div><h3>The Translational Potential of this Article</h3><p>The study demonstrated that the r","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214031X24000044/pdfft?md5=792e27fdd18e760b0f3decbf619da968&pid=1-s2.0-S2214031X24000044-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140308814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-01DOI: 10.1016/j.jot.2024.04.001
Gang Li
{"title":"Basic research is the foundation and driving force for clinical translation","authors":"Gang Li","doi":"10.1016/j.jot.2024.04.001","DOIUrl":"https://doi.org/10.1016/j.jot.2024.04.001","url":null,"abstract":"","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214031X24000329/pdfft?md5=640d1b149179b4d7b2e34c9ec8b91663&pid=1-s2.0-S2214031X24000329-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140557932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-01DOI: 10.1016/j.jot.2023.12.006
Baoqi Li , Pascal Thebault , Béatrice Labat , Guy Ladam , Volker Alt , Markus Rupp , Christoph Brochausen , Jonathan Jantsch , Margaret Ip , Ning Zhang , Wing-Hoi Cheung , Shui Yee Sharon Leung , Ronald Man Yeung Wong
Objective
Fracture-related infection (FRI) remains a major concern in orthopaedic trauma. Functionalizing implants with antibacterial coatings are a promising strategy in mitigating FRI. Numerous implant coatings have been reported but the preventive and therapeutic effects vary. This systematic review aimed to provide a comprehensive overview of current implant coating strategies to prevent and treat FRI in animal fracture and bone defect models.
Methods
A literature search was performed in three databases: PubMed, Web of Science and Embase, with predetermined keywords and criteria up to 28 February 2023. Preclinical studies on implant coatings in animal fracture or defect models that assessed antibacterial and bone healing effects were included.
Results
A total of 14 studies were included in this systematic review, seven of which used fracture models and seven used defect models. Passive coatings with bacteria adhesion resistance were investigated in two studies. Active coatings with bactericidal effects were investigated in 12 studies, four of which used metal ions including Ag+ and Cu2+; five studies used antibiotics including chlorhexidine, tigecycline, vancomycin, and gentamicin sulfate; and the other three studies used natural antibacterial materials including chitosan, antimicrobial peptides, and lysostaphin. Overall, these implant coatings exhibited promising efficacy in antibacterial effects and bone formation.
Conclusion
Antibacterial coating strategies reduced bacterial infections in animal models and favored bone healing in vivo. Future studies of implant coatings should focus on optimal biocompatibility, antibacterial effects against multi-drug resistant bacteria and polymicrobial infections, and osseointegration and osteogenesis promotion especially in osteoporotic bone by constructing multi-functional coatings for FRI therapy.
The translational potential of this paper
The clinical treatment of FRI is complex and challenging. This review summarizes novel orthopaedic implant coating strategies applied to FRI in preclinical studies, and offers a perspective on the future development of orthopaedic implant coatings, which can potentially contribute to alternative strategies in clinical practice.
{"title":"Implants coating strategies for antibacterial treatment in fracture and defect models: A systematic review of animal studies","authors":"Baoqi Li , Pascal Thebault , Béatrice Labat , Guy Ladam , Volker Alt , Markus Rupp , Christoph Brochausen , Jonathan Jantsch , Margaret Ip , Ning Zhang , Wing-Hoi Cheung , Shui Yee Sharon Leung , Ronald Man Yeung Wong","doi":"10.1016/j.jot.2023.12.006","DOIUrl":"https://doi.org/10.1016/j.jot.2023.12.006","url":null,"abstract":"<div><h3>Objective</h3><p>Fracture-related infection (FRI) remains a major concern in orthopaedic trauma. Functionalizing implants with antibacterial coatings are a promising strategy in mitigating FRI. Numerous implant coatings have been reported but the preventive and therapeutic effects vary. This systematic review aimed to provide a comprehensive overview of current implant coating strategies to prevent and treat FRI in animal fracture and bone defect models.</p></div><div><h3>Methods</h3><p>A literature search was performed in three databases: PubMed, Web of Science and Embase, with predetermined keywords and criteria up to 28 February 2023. Preclinical studies on implant coatings in animal fracture or defect models that assessed antibacterial and bone healing effects were included.</p></div><div><h3>Results</h3><p>A total of 14 studies were included in this systematic review, seven of which used fracture models and seven used defect models. Passive coatings with bacteria adhesion resistance were investigated in two studies. Active coatings with bactericidal effects were investigated in 12 studies, four of which used metal ions including Ag<sup>+</sup> and Cu<sup>2+</sup>; five studies used antibiotics including chlorhexidine, tigecycline, vancomycin, and gentamicin sulfate; and the other three studies used natural antibacterial materials including chitosan, antimicrobial peptides, and lysostaphin. Overall, these implant coatings exhibited promising efficacy in antibacterial effects and bone formation.</p></div><div><h3>Conclusion</h3><p>Antibacterial coating strategies reduced bacterial infections in animal models and favored bone healing <em>in vivo</em>. Future studies of implant coatings should focus on optimal biocompatibility, antibacterial effects against multi-drug resistant bacteria and polymicrobial infections, and osseointegration and osteogenesis promotion especially in osteoporotic bone by constructing multi-functional coatings for FRI therapy.</p></div><div><h3>The translational potential of this paper</h3><p>The clinical treatment of FRI is complex and challenging. This review summarizes novel orthopaedic implant coating strategies applied to FRI in preclinical studies, and offers a perspective on the future development of orthopaedic implant coatings, which can potentially contribute to alternative strategies in clinical practice.</p></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214031X24000020/pdfft?md5=44f5f4a1c05f8e8ebf3f724e88fd33d9&pid=1-s2.0-S2214031X24000020-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140062109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cartilage tissue engineering faces challenges related to the use of scaffolds and limited seed cells. This study aims to propose a cost-effective and straightforward approach using costal chondrocytes (CCs) as an alternative cell source to overcome these challenges, eliminating the need for special culture equipment or scaffolds.
Methods
CCs were cultured at a high cell density with and without ascorbic acid treatment, serving as the experimental and control groups, respectively. Viability and tissue-engineered constructs (TEC) formation were evaluated until day 14. Slices of TEC samples were used for histological staining to evaluate the secretion of glycosaminoglycans and different types of collagen proteins within the extracellular matrix. mRNA sequencing and qPCR were performed to examine gene expression related to cartilage matrix secretion in the chondrocytes. In vivo experiments were conducted by implanting TECs from different groups into the defect site, followed by sample collection after 12 weeks for histological staining and scoring to evaluate the extent of cartilage regeneration. Hematoxylin-eosin (HE), Safranin-O-Fast Green, and Masson's trichrome stainings were used to examine the content of cartilage-related matrix components in the in vivo repair tissue. Immunohistochemical staining for type I and type II collagen, as well as aggrecan, was performed to assess the presence and distribution of these specific markers. Additionally, immunohistochemical staining for type X collagen was used to observe any hypertrophic changes in the repaired tissue.
Results
Viability of the chondrocytes remained high throughout the culture period, and the TECs displayed an enriched extracellular matrix suitable for surgical procedures. In vitro study revealed glycosaminoglycan and type II collagen production in both groups of TEC, while the TEC matrix treated with ascorbic acid displayed greater abundance. The results of mRNA sequencing and qPCR showed that genes related to cartilage matrix secretion such as Sox9, Col2, and Acan were upregulated by ascorbic acid in costal chondrocytes. Although the addition of Asc-2P led to an increase in COL10 expression according to qPCR and RNA-seq results, the immunofluorescence staining results of the two groups of TECs exhibited similar distribution and fluorescence intensity. In vivo experiments showed that both groups of TEC could adhere to the defect sites and kept hyaline cartilage morphology until 12 weeks. TEC treated with ascorbic acid showed superior cartilage regeneration as evidenced by significantly higher ICRS and O'Driscoll scores and stronger Safranin-O and collagen staining mimicking native cartilage when compared to other groups. In addition, the immunohistochemical staining results of Collgan X indicated that, after 12 weeks, the ascorbic acid-treated TEC did not exhibit further hypertrophy upon transplantation into the
{"title":"Enhanced articular cartilage regeneration using costal chondrocyte-derived scaffold-free tissue engineered constructs with ascorbic acid treatment","authors":"Kaiwen Zheng, Yiyang Ma, Cheng Chiu, Mengxin Xue, Changqing Zhang, Dajiang Du","doi":"10.1016/j.jot.2024.02.005","DOIUrl":"https://doi.org/10.1016/j.jot.2024.02.005","url":null,"abstract":"<div><h3>Background</h3><p>Cartilage tissue engineering faces challenges related to the use of scaffolds and limited seed cells. This study aims to propose a cost-effective and straightforward approach using costal chondrocytes (CCs) as an alternative cell source to overcome these challenges, eliminating the need for special culture equipment or scaffolds.</p></div><div><h3>Methods</h3><p>CCs were cultured at a high cell density with and without ascorbic acid treatment, serving as the experimental and control groups, respectively. Viability and tissue-engineered constructs (TEC) formation were evaluated until day 14. Slices of TEC samples were used for histological staining to evaluate the secretion of glycosaminoglycans and different types of collagen proteins within the extracellular matrix. mRNA sequencing and qPCR were performed to examine gene expression related to cartilage matrix secretion in the chondrocytes. In vivo experiments were conducted by implanting TECs from different groups into the defect site, followed by sample collection after 12 weeks for histological staining and scoring to evaluate the extent of cartilage regeneration. Hematoxylin-eosin (HE), Safranin-O-Fast Green, and Masson's trichrome stainings were used to examine the content of cartilage-related matrix components in the in vivo repair tissue. Immunohistochemical staining for type I and type II collagen, as well as aggrecan, was performed to assess the presence and distribution of these specific markers. Additionally, immunohistochemical staining for type X collagen was used to observe any hypertrophic changes in the repaired tissue.</p></div><div><h3>Results</h3><p>Viability of the chondrocytes remained high throughout the culture period, and the TECs displayed an enriched extracellular matrix suitable for surgical procedures. In vitro study revealed glycosaminoglycan and type II collagen production in both groups of TEC, while the TEC matrix treated with ascorbic acid displayed greater abundance. The results of mRNA sequencing and qPCR showed that genes related to cartilage matrix secretion such as Sox9, Col2, and Acan were upregulated by ascorbic acid in costal chondrocytes. Although the addition of Asc-2P led to an increase in COL10 expression according to qPCR and RNA-seq results, the immunofluorescence staining results of the two groups of TECs exhibited similar distribution and fluorescence intensity. In vivo experiments showed that both groups of TEC could adhere to the defect sites and kept hyaline cartilage morphology until 12 weeks. TEC treated with ascorbic acid showed superior cartilage regeneration as evidenced by significantly higher ICRS and O'Driscoll scores and stronger Safranin-O and collagen staining mimicking native cartilage when compared to other groups. In addition, the immunohistochemical staining results of Collgan X indicated that, after 12 weeks, the ascorbic acid-treated TEC did not exhibit further hypertrophy upon transplantation into the","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2214031X24000214/pdfft?md5=b5653bc7717622e4f9f85e1876984c0c&pid=1-s2.0-S2214031X24000214-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140187854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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