首页 > 最新文献

Journal of Orthopaedic Translation最新文献

英文 中文
New developments in osteoporosis, osteoarthritis and soft tissue repair 骨质疏松、骨关节炎和软组织修复的新进展。
IF 5.9 1区 医学 Q1 ORTHOPEDICS Pub Date : 2024-11-01 DOI: 10.1016/j.jot.2024.11.002
Gang Li (Prof)
{"title":"New developments in osteoporosis, osteoarthritis and soft tissue repair","authors":"Gang Li (Prof)","doi":"10.1016/j.jot.2024.11.002","DOIUrl":"10.1016/j.jot.2024.11.002","url":null,"abstract":"","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"49 ","pages":"Pages A1-A2"},"PeriodicalIF":5.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11681327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903094","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}
引用次数: 0
Corrigendum to ‘Osteostaticytes: A novel osteoclast subset couples bone resorption and bone formation’[Journal of Orthopaedic Translation 47 (2024) 144–160] 对“Osteostaticytes:一种新的破骨细胞亚群耦合骨吸收和骨形成”的更正[Journal of Orthopaedic Translation 47(2024) 144-160]。
IF 5.9 1区 医学 Q1 ORTHOPEDICS Pub Date : 2024-11-01 DOI: 10.1016/j.jot.2024.08.018
Zhiyuan Wei , Jian Zhou , Jie Shen , Dong Sun , Tianbao Gao , Qin Liu , Hongri Wu , Xiaohua Wang , Shulin Wang , Shiyu Xiao , Chao Han , Di Yang , Hui Dong , Yuzhang Wu , Yi Zhang , Shuai Xu , Xian Wang , Jie Luo , Qijie Dai , Jun Zhu , Zhao Xie
{"title":"Corrigendum to ‘Osteostaticytes: A novel osteoclast subset couples bone resorption and bone formation’[Journal of Orthopaedic Translation 47 (2024) 144–160]","authors":"Zhiyuan Wei , Jian Zhou , Jie Shen , Dong Sun , Tianbao Gao , Qin Liu , Hongri Wu , Xiaohua Wang , Shulin Wang , Shiyu Xiao , Chao Han , Di Yang , Hui Dong , Yuzhang Wu , Yi Zhang , Shuai Xu , Xian Wang , Jie Luo , Qijie Dai , Jun Zhu , Zhao Xie","doi":"10.1016/j.jot.2024.08.018","DOIUrl":"10.1016/j.jot.2024.08.018","url":null,"abstract":"","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"49 ","pages":"Pages 339-340"},"PeriodicalIF":5.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11681331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903086","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}
引用次数: 0
Recent developments in Achilles tendon risk-analyzing rupture factors for enhanced injury prevention and clinical guidance: Current implications of regenerative medicine 跟腱风险分析断裂因素的最新进展,以加强损伤预防和临床指导:再生医学的当前影响
IF 5.9 1区 医学 Q1 ORTHOPEDICS Pub Date : 2024-11-01 DOI: 10.1016/j.jot.2024.08.024
Maria V. Sankova , Narasimha M. Beeraka , Marine V. Oganesyan , Negoriya A. Rizaeva , Aleksey V. Sankov , Olga S. Shelestova , Kirill V. Bulygin , Hemanth Vikram PR , A.N. Barinov , A.K. Khalimova , Y. Padmanabha Reddy , Basappa Basappa , Vladimir N. Nikolenko
<div><h3>Background</h3><div>In recent years, many countries have actively implemented programs and strategies to promote physical education and sports. Despite these efforts, the increase in physical activity has been accompanied by a significant rise in muscle and tendon-ligament injuries, with Achilles tendon rupture being the most prevalent, accounting for 47 % of such injuries. This review aims to summarize all significant factors determining the predisposition of the Achilles tendon to rupture, to develop effective personalized prevention measures.</div></div><div><h3>Objective</h3><div>To identify and evaluate the risk factors contributing to Achilles tendon rupture and to develop strategies for personalized prevention.</div></div><div><h3>Methods</h3><div>This review utilized data from several databases, including Elsevier, Global Health, PubMed-NCBI, Embase, Medline, Scopus, ResearchGate, RSCI, Cochrane Library, Google Scholar, eLibrary.ru, and CyberLeninka. Both non-modifiable and modifiable risk factors for Achilles tendon injuries and ruptures were analyzed.</div></div><div><h3>Results</h3><div>The analysis identified several non-modifiable risk factors, such as genetic predisposition, anatomical and functional features of the Achilles tendon, sex, and age. These factors should be considered when selecting sports activities and designing training programs. Modifiable risk factors included imbalanced nutrition, improper exercise regimens, and inadequate monitoring of Achilles tendon conditions in athletes. Early treatment of musculoskeletal injuries, Achilles tendon diseases, foot deformities, and metabolic disorders is crucial. Long-term drug use and its risk assessment were also highlighted as important considerations. Furthermore, recent clinical advancements in both conventional and surgical methods to treat Achilles tendon injuries were described. The efficacy of these therapies in enhancing functional outcomes in individuals with Achilles injuries was compared. Advancements in cell-based and scaffold-based therapies aimed at enhancing cell regeneration and repairing Achilles injuries were also discussed.</div></div><div><h3>Discussion</h3><div>The combination of several established factors significantly increases the risk of Achilles tendon rupture. Addressing these factors through personalized prevention strategies can effectively reduce the incidence of these injuries. Proper nutrition, regular monitoring, timely treatment, and the correction of metabolic disorders are essential components of a comprehensive prevention plan.</div></div><div><h3>Conclusion</h3><div>Early identification of Achilles tendon risk factors allows for the timely development of effective personalized prevention strategies. These measures can contribute significantly to public health preservation by reducing the incidence of Achilles tendon ruptures associated with physical activity and sports. Continued research and clinical advancements in treatment me
背景近年来,许多国家都在积极实施推广体育运动的计划和战略。尽管做出了这些努力,但伴随着体育锻炼的增加,肌肉和肌腱韧带损伤也显著增加,其中跟腱断裂最为常见,占此类损伤的 47%。本综述旨在总结决定跟腱断裂易感性的所有重要因素,以制定有效的个性化预防措施。方法本综述利用了多个数据库中的数据,包括 Elsevier、Global Health、PubMed-NCBI、Embase、Medline、Scopus、ResearchGate、RSCI、Cochrane Library、Google Scholar、eLibrary.ru 和 CyberLeninka。分析了跟腱损伤和断裂的不可改变和可改变的风险因素。结果分析发现了一些不可改变的风险因素,如遗传倾向、跟腱的解剖和功能特征、性别和年龄。在选择运动项目和设计训练计划时应考虑这些因素。可改变的风险因素包括营养失衡、运动方案不当以及对运动员跟腱状况的监测不足。及早治疗肌肉骨骼损伤、跟腱疾病、足部畸形和代谢紊乱至关重要。长期用药及其风险评估也是重要的考虑因素。此外,还介绍了治疗跟腱损伤的传统方法和手术方法的最新临床进展。比较了这些疗法在提高跟腱损伤患者功能疗效方面的功效。此外,还讨论了以细胞和支架为基础的疗法在促进细胞再生和修复跟腱损伤方面的进展。通过个性化的预防策略来解决这些因素,可以有效降低这些损伤的发生率。适当的营养、定期监测、及时治疗和纠正代谢紊乱是全面预防计划的重要组成部分。这些措施可以降低与体力活动和体育运动相关的跟腱断裂发病率,从而为保护公众健康做出重大贡献。本文的转化潜力本研究确定了跟腱损伤的主要可调节和不可调节风险因素,为个性化预防策略铺平了道路。强调营养、锻炼和肌肉骨骼问题的早期治疗,以及基于细胞的疗法的进步,为改善恢复和疗效提供了前景广阔的途径。这些发现可以指导预防和康复方面的临床实践,最终减少跟腱损伤,提高公众健康水平。
{"title":"Recent developments in Achilles tendon risk-analyzing rupture factors for enhanced injury prevention and clinical guidance: Current implications of regenerative medicine","authors":"Maria V. Sankova ,&nbsp;Narasimha M. Beeraka ,&nbsp;Marine V. Oganesyan ,&nbsp;Negoriya A. Rizaeva ,&nbsp;Aleksey V. Sankov ,&nbsp;Olga S. Shelestova ,&nbsp;Kirill V. Bulygin ,&nbsp;Hemanth Vikram PR ,&nbsp;A.N. Barinov ,&nbsp;A.K. Khalimova ,&nbsp;Y. Padmanabha Reddy ,&nbsp;Basappa Basappa ,&nbsp;Vladimir N. Nikolenko","doi":"10.1016/j.jot.2024.08.024","DOIUrl":"10.1016/j.jot.2024.08.024","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;In recent years, many countries have actively implemented programs and strategies to promote physical education and sports. Despite these efforts, the increase in physical activity has been accompanied by a significant rise in muscle and tendon-ligament injuries, with Achilles tendon rupture being the most prevalent, accounting for 47 % of such injuries. This review aims to summarize all significant factors determining the predisposition of the Achilles tendon to rupture, to develop effective personalized prevention measures.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;To identify and evaluate the risk factors contributing to Achilles tendon rupture and to develop strategies for personalized prevention.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;This review utilized data from several databases, including Elsevier, Global Health, PubMed-NCBI, Embase, Medline, Scopus, ResearchGate, RSCI, Cochrane Library, Google Scholar, eLibrary.ru, and CyberLeninka. Both non-modifiable and modifiable risk factors for Achilles tendon injuries and ruptures were analyzed.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;The analysis identified several non-modifiable risk factors, such as genetic predisposition, anatomical and functional features of the Achilles tendon, sex, and age. These factors should be considered when selecting sports activities and designing training programs. Modifiable risk factors included imbalanced nutrition, improper exercise regimens, and inadequate monitoring of Achilles tendon conditions in athletes. Early treatment of musculoskeletal injuries, Achilles tendon diseases, foot deformities, and metabolic disorders is crucial. Long-term drug use and its risk assessment were also highlighted as important considerations. Furthermore, recent clinical advancements in both conventional and surgical methods to treat Achilles tendon injuries were described. The efficacy of these therapies in enhancing functional outcomes in individuals with Achilles injuries was compared. Advancements in cell-based and scaffold-based therapies aimed at enhancing cell regeneration and repairing Achilles injuries were also discussed.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Discussion&lt;/h3&gt;&lt;div&gt;The combination of several established factors significantly increases the risk of Achilles tendon rupture. Addressing these factors through personalized prevention strategies can effectively reduce the incidence of these injuries. Proper nutrition, regular monitoring, timely treatment, and the correction of metabolic disorders are essential components of a comprehensive prevention plan.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;Early identification of Achilles tendon risk factors allows for the timely development of effective personalized prevention strategies. These measures can contribute significantly to public health preservation by reducing the incidence of Achilles tendon ruptures associated with physical activity and sports. Continued research and clinical advancements in treatment me","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"49 ","pages":"Pages 289-307"},"PeriodicalIF":5.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142578322","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}
引用次数: 0
Innovative development of robot reduction system in geriatric pelvic fractures: A single-center case series in Beijing, China 老年骨盆骨折机器人复位系统的创新发展:中国北京单中心病例系列
IF 5.9 1区 医学 Q1 ORTHOPEDICS Pub Date : 2024-11-01 DOI: 10.1016/j.jot.2024.08.023
Chunpeng Zhao , Honghu Xiao , Qiyong Cao , Yufeng Ge , Yuneng Li , Yu Wang , Gang Zhu , Xinbao Wu
Displaced fragility fractures of the pelvis (FFP) pose significant challenges in orthopaedic trauma, owing to patient comorbidities, deteriorating bone quality, and surgical complexities. Despite technological advancements, no robotic methods have been documented for displaced FFP management. To address this, we introduced an advanced robot-assisted fracture reduction system, comprising a tracking device, path planning software, and robotic arms. This study evaluated fifteen consecutive patients with displaced FFP (average age 80.4 ± 9.1 years), who underwent robot-assisted reduction and internal fixation (RARIF) between January 2022 and May 2023. All were categorized as Rommens FFP type III, with a median time of 6 days (range 4–11) from injury to surgery. Operative times averaged 165 ± 44 min, with median blood loss of 50 mL. Postoperative radiographs showed all patients achieved excellent or good reductions as per Matta criteria, marking a 100 % success rate. A 6-month follow-up revealed an average modified Majeed score of 81.4, with 85.7 % of patients rated excellent or good. All fractures healed without complications. Leveraging our intelligent system, RARIF proves to be a safe and effective approach for displaced FFP, facilitating postoperative pain alleviation and early mobilization despite compromised health and bone conditions. This approach may revolutionize the management of FFP in an increasingly aging population, signaling a significant shift in therapeutic strategies.
Translational Potential of this Article: Elderly patients with displaced FFP often present complex surgical challenges due to comorbidities and poor bone quality, complicating reduction procedures and often leading to ineffective fixation. Addressing these challenges, we have developed an innovative robot-assisted fracture reduction system, offering a practical alternative to conventional methods. This system optimizes the applied force and direction during the reduction process, thereby reducing the needs for manual and repetitive attempts. Our report, detailing the successful implementation of this technique in 15 FFP cases, signifies a considerable leap forward in the field of orthopaedic surgery. This technique notably benefits the elderly population, a group traditionally marginalized in receiving care for complex orthopedic conditions.
骨盆移位性脆性骨折(FFP)给创伤骨科带来了巨大挑战,这是因为患者合并症多、骨质不断恶化以及手术复杂。尽管技术在不断进步,但目前还没有用于治疗骨盆移位性骨折的机器人方法。为此,我们引进了先进的机器人辅助骨折复位系统,该系统由跟踪装置、路径规划软件和机械臂组成。本研究对 2022 年 1 月至 2023 年 5 月间接受机器人辅助骨折复位和内固定术(RARIF)的 15 名移位 FFP 患者(平均年龄为 80.4 ± 9.1 岁)进行了评估。所有患者均被归为罗门氏 FFP III 型,从受伤到手术的中位时间为 6 天(4-11 天不等)。手术时间平均为 165 ± 44 分钟,中位失血量为 50 毫升。术后X光片显示,根据Matta标准,所有患者都达到了极佳或良好的缩小效果,成功率为100%。6 个月的随访显示,改良的 Majeed 评分平均为 81.4 分,85.7% 的患者被评为优或良。所有骨折均愈合,无并发症。利用我们的智能系统,RARIF 被证明是治疗移位的 FFP 的一种安全有效的方法,尽管患者的健康状况和骨骼条件受到损害,但它仍能减轻术后疼痛并促进早期活动。这种方法可能会彻底改变对日益老龄化的人群中 FFP 的管理,标志着治疗策略的重大转变:由于合并症和骨质差,移位的FFP老年患者往往面临复杂的手术挑战,使还原手术复杂化,往往导致固定效果不佳。为了应对这些挑战,我们开发了一种创新的机器人辅助骨折复位系统,为传统方法提供了一种实用的替代方案。该系统能优化骨折复位过程中的作用力和方向,从而减少人工操作和重复尝试的需要。我们的报告详细介绍了这项技术在 15 例 FFP 病例中的成功应用,标志着骨科手术领域的重大飞跃。这项技术明显惠及老年人群,而这一群体在接受复杂骨科疾病治疗时历来被边缘化。
{"title":"Innovative development of robot reduction system in geriatric pelvic fractures: A single-center case series in Beijing, China","authors":"Chunpeng Zhao ,&nbsp;Honghu Xiao ,&nbsp;Qiyong Cao ,&nbsp;Yufeng Ge ,&nbsp;Yuneng Li ,&nbsp;Yu Wang ,&nbsp;Gang Zhu ,&nbsp;Xinbao Wu","doi":"10.1016/j.jot.2024.08.023","DOIUrl":"10.1016/j.jot.2024.08.023","url":null,"abstract":"<div><div>Displaced fragility fractures of the pelvis (FFP) pose significant challenges in orthopaedic trauma, owing to patient comorbidities, deteriorating bone quality, and surgical complexities. Despite technological advancements, no robotic methods have been documented for displaced FFP management. To address this, we introduced an advanced robot-assisted fracture reduction system, comprising a tracking device, path planning software, and robotic arms. This study evaluated fifteen consecutive patients with displaced FFP (average age 80.4 ± 9.1 years), who underwent robot-assisted reduction and internal fixation (RARIF) between January 2022 and May 2023. All were categorized as Rommens FFP type III, with a median time of 6 days (range 4–11) from injury to surgery. Operative times averaged 165 ± 44 min, with median blood loss of 50 mL. Postoperative radiographs showed all patients achieved excellent or good reductions as per Matta criteria, marking a 100 % success rate. A 6-month follow-up revealed an average modified Majeed score of 81.4, with 85.7 % of patients rated excellent or good. All fractures healed without complications. Leveraging our intelligent system, RARIF proves to be a safe and effective approach for displaced FFP, facilitating postoperative pain alleviation and early mobilization despite compromised health and bone conditions. This approach may revolutionize the management of FFP in an increasingly aging population, signaling a significant shift in therapeutic strategies.</div><div>Translational Potential of this Article: Elderly patients with displaced FFP often present complex surgical challenges due to comorbidities and poor bone quality, complicating reduction procedures and often leading to ineffective fixation. Addressing these challenges, we have developed an innovative robot-assisted fracture reduction system, offering a practical alternative to conventional methods. This system optimizes the applied force and direction during the reduction process, thereby reducing the needs for manual and repetitive attempts. Our report, detailing the successful implementation of this technique in 15 FFP cases, signifies a considerable leap forward in the field of orthopaedic surgery. This technique notably benefits the elderly population, a group traditionally marginalized in receiving care for complex orthopedic conditions.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"49 ","pages":"Pages 283-288"},"PeriodicalIF":5.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142554142","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}
引用次数: 0
Sensory nerve EP4 facilitates heterotopic ossification by regulating angiogenesis-coupled bone formation 感觉神经EP4通过调节血管生成耦合骨形成促进异位骨化
IF 5.9 1区 医学 Q1 ORTHOPEDICS Pub Date : 2024-11-01 DOI: 10.1016/j.jot.2024.09.005
Rongmin Lin , Hancheng Lin , Chencheng Zhu , Jieming Zeng , Jiahui Hou , Ting Xu , Yihui Tan , Xuyou Zhou , Yuan Ma , Mankai Yang , Kuanhai Wei , Bin Yu , Hangtian Wu , Zhuang Cui

Objective

Heterotopic ossification (HO) refers to the abnormal development of bone in soft tissue rather than within bone itself. Previous research has shown that sensory nerve prostaglandin E2 receptor 4 (EP4) signaling not only governs pain perception but also influences bone formation. However, the relationship between sensory nerve EP4 and the pathogenesis of HO in the Achilles tendon remains unclear. This study aims to investigate this relationship and the underlying mechanisms.

Methods

We generated sensory nerve EP4-specific knockout mice, with the genotype of Avil-CreEP4fl/fl, was propagated. Transcriptome sequencing and bioinformatics analysis techniques were used to identify the potential molecular pathways involving with sensory nerve EP4. Additionally, a neurectomy mouse model was created by transecting the sciatic nerve transection, to examine the effects and mechanisms of peripheral innervation on HO in vivo. Micro-CT, immunofluorescence (IF), Hematoxylin and Eosin (H&E) Staining, Safranin O-Fast Green staining and western blotting were used to analyze changes in cellular and tissue components.

Results

We here observed an increase in sensory nerve EP4 and H-type vessels during the pathogenesis of HO in both human subjects and mice. Proximal neurectomy through sciatic nerve transection or the targeted knockout of EP4 in sensory nerves hindered angiogenesis-dependent bone formation and the development of HO at the traumatic site of the Achilles tendon. Furthermore, we identified the Efnb2 (Ephrin-B2)/Dll4 (Delta-like ligand 4) axis as a potential downstream element influenced by sensory nerve EP4 in the regulation of HO. Notably, administration of an EP4 inhibitor demonstrated the ability to alleviate HO. Based on these findings, sensory nerve EP4 emerges as an innovative and promising approach for managing HO.

Conclusion

Our findings demonstrate that the sensory nerve EP4 promotes ectopic bone formation by modulating angiogenesis-associated osteogenesis during HO.

The translational potential of this article

Our results provide a mechanistic rationale for targeting sensory nerve EP4 as a promising candidate for HO therapy.
目的异位骨化(HO)是指骨骼在软组织内而非骨骼本身的异常发育。以往的研究表明,感觉神经前列腺素 E2 受体 4(EP4)信号不仅能控制痛觉,还能影响骨形成。然而,感觉神经EP4与跟腱HO发病机制之间的关系仍不清楚。本研究旨在探讨这种关系及其内在机制。方法我们繁殖了基因型为Avil-CreEP4fl/fl的感觉神经EP4特异性基因敲除小鼠。我们利用转录组测序和生物信息学分析技术确定了涉及感觉神经 EP4 的潜在分子通路。此外,还通过横断坐骨神经建立了神经切除小鼠模型,以研究体内外周神经支配对 HO 的影响和机制。研究采用显微 CT、免疫荧光 (IF)、苏木精和伊红 (H&E) 染色、沙弗宁 O-Fast Green 染色和 Western 印迹技术分析细胞和组织成分的变化。通过坐骨神经横断进行的近端神经切除术或靶向敲除感觉神经中的EP4阻碍了血管生成依赖性骨形成以及跟腱创伤部位HO的发展。此外,我们还发现Efnb2(Ephrin-B2)/Dll4(Delta-like ligand 4)轴是受感觉神经EP4影响的一个潜在下游元素,它在HO的调控过程中起着重要作用。值得注意的是,服用 EP4 抑制剂能够缓解 HO。结论我们的研究结果表明,感觉神经EP4在HO过程中通过调节血管生成相关的骨生成促进了异位骨的形成。
{"title":"Sensory nerve EP4 facilitates heterotopic ossification by regulating angiogenesis-coupled bone formation","authors":"Rongmin Lin ,&nbsp;Hancheng Lin ,&nbsp;Chencheng Zhu ,&nbsp;Jieming Zeng ,&nbsp;Jiahui Hou ,&nbsp;Ting Xu ,&nbsp;Yihui Tan ,&nbsp;Xuyou Zhou ,&nbsp;Yuan Ma ,&nbsp;Mankai Yang ,&nbsp;Kuanhai Wei ,&nbsp;Bin Yu ,&nbsp;Hangtian Wu ,&nbsp;Zhuang Cui","doi":"10.1016/j.jot.2024.09.005","DOIUrl":"10.1016/j.jot.2024.09.005","url":null,"abstract":"<div><h3>Objective</h3><div>Heterotopic ossification (HO) refers to the abnormal development of bone in soft tissue rather than within bone itself. Previous research has shown that sensory nerve prostaglandin E2 receptor 4 (EP4) signaling not only governs pain perception but also influences bone formation. However, the relationship between sensory nerve EP4 and the pathogenesis of HO in the Achilles tendon remains unclear. This study aims to investigate this relationship and the underlying mechanisms.</div></div><div><h3>Methods</h3><div>We generated sensory nerve EP4-specific knockout mice, with the genotype of Avil-CreEP4<sup>fl/fl</sup>, was propagated. Transcriptome sequencing and bioinformatics analysis techniques were used to identify the potential molecular pathways involving with sensory nerve EP4. Additionally, a neurectomy mouse model was created by transecting the sciatic nerve transection, to examine the effects and mechanisms of peripheral innervation on HO in vivo. Micro-CT, immunofluorescence (IF), Hematoxylin and Eosin (H&amp;E) Staining, Safranin O-Fast Green staining and western blotting were used to analyze changes in cellular and tissue components.</div></div><div><h3>Results</h3><div>We here observed an increase in sensory nerve EP4 and H-type vessels during the pathogenesis of HO in both human subjects and mice. Proximal neurectomy through sciatic nerve transection or the targeted knockout of EP4 in sensory nerves hindered angiogenesis-dependent bone formation and the development of HO at the traumatic site of the Achilles tendon. Furthermore, we identified the Efnb2 (Ephrin-B2)/Dll4 (Delta-like ligand 4) axis as a potential downstream element influenced by sensory nerve EP4 in the regulation of HO. Notably, administration of an EP4 inhibitor demonstrated the ability to alleviate HO. Based on these findings, sensory nerve EP4 emerges as an innovative and promising approach for managing HO.</div></div><div><h3>Conclusion</h3><div>Our findings demonstrate that the sensory nerve EP4 promotes ectopic bone formation by modulating angiogenesis-associated osteogenesis during HO.</div></div><div><h3>The translational potential of this article</h3><div>Our results provide a mechanistic rationale for targeting sensory nerve EP4 as a promising candidate for HO therapy.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"49 ","pages":"Pages 325-338"},"PeriodicalIF":5.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142587282","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}
引用次数: 0
Corrigendum to ‘YAP maintains cartilage stem/progenitor cell homeostasis in osteoarthritis’[Journal of Orthopaedic Translation 46 (2024) 79–90] “YAP维持骨关节炎软骨干细胞/祖细胞稳态”的更正[Journal of Orthopaedic Translation 46(2024) 79-90]。
IF 5.9 1区 医学 Q1 ORTHOPEDICS Pub Date : 2024-11-01 DOI: 10.1016/j.jot.2024.08.021
Lina Zhang , Xinxing Wang , Guang Xia , Junjie Huang , Zi Wen , Chi Liang , Xu Cao , Yong Zhou , Song Wu
{"title":"Corrigendum to ‘YAP maintains cartilage stem/progenitor cell homeostasis in osteoarthritis’[Journal of Orthopaedic Translation 46 (2024) 79–90]","authors":"Lina Zhang ,&nbsp;Xinxing Wang ,&nbsp;Guang Xia ,&nbsp;Junjie Huang ,&nbsp;Zi Wen ,&nbsp;Chi Liang ,&nbsp;Xu Cao ,&nbsp;Yong Zhou ,&nbsp;Song Wu","doi":"10.1016/j.jot.2024.08.021","DOIUrl":"10.1016/j.jot.2024.08.021","url":null,"abstract":"","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"49 ","pages":"Page 341"},"PeriodicalIF":5.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11681330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903089","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}
引用次数: 0
Mesoporous bioactive glass-enhanced MSC-derived exosomes promote bone regeneration and immunomodulation in vitro and in vivo 介孔生物活性玻璃增强间充质干细胞衍生外泌体在体外和体内促进骨再生和免疫调节
IF 5.9 1区 医学 Q1 ORTHOPEDICS Pub Date : 2024-10-29 DOI: 10.1016/j.jot.2024.09.009
Qingde Wa , Yongxiang Luo , Yubo Tang , Jiaxiang Song , Penghui Zhang , Xitao Linghu , Sien Lin , Gang Li , Yixiao Wang , Zhenyu Wen , Shuai Huang , Weikang Xu

Background

Exosomes produced by mesenchymal stem cells (MSCs) have vascular generative properties and are considered new effective candidates for the treatment of bone defects as alternatives to cell therapy. Improving the pro-regenerative function and efficacy of exosomes has been a popular research topic in the field of orthopaedics.

Methods

We prepared mesoporous bioactive glass (mBG) microspheres via the template method. The ionic products of mBGs used to treat MSCs were extracted, and the effects of exosomes secreted by MSCs on osteoblast (OB) and macrophage (MP) behaviour and bone defect repair were observed in vivo (Micro-CT, H&E, Masson, and immunofluorescence staining for BMP2, COL1, VEGF, CD31, CD163, and iNOS).

Results

The mBG spheres were successfully prepared, and the Exo-mBG were isolated and extracted. Compared with those in the blank and Exo-Con groups, the proliferation and osteogenic differentiation of OBs in the Exo-mBG group were significantly greater. For example, on Day 7, OPN gene expression in the Ctrl-Exo group was 3.97 and 2.83 times greater than that in the blank and Exo-mBG groups, respectively. In a cranial defect rat model, Exo-mBG promoted bone tissue healing and angiogenesis, increased M2 macrophage polarisation and inhibited M1 macrophage polarisation, as verified by micro-CT, H&E staining, Masson staining and immunofluorescence staining. These effects may be due to the combination of a higher silicon concentration and a higher calcium-to-phosphorus ratio in the mBG ionic products.

Conclusion

This study provides insights for the application of exosomes in cell-free therapy and a new scientific basis and technical approach for the utilisation of MSC-derived exosomes in bone defect repair.

The translational potential of this article

Our study demonstrated that exosomes produced by mBG-stimulated MSCs have excellent in vitro and in vivo bone-enabling and immunomodulatory functions and provides insights into the use of exosomes in clinical cell-free therapies.
背景间充质干细胞(MSCs)产生的外泌体具有血管生成特性,被认为是替代细胞疗法治疗骨缺损的新有效候选物质。方法我们通过模板法制备了介孔生物活性玻璃(mBG)微球。结果成功制备了mBG微球,并分离提取了Exo-mBG。与空白组和 Exo-Con 组相比,Exo-mBG 组 OB 的增殖和成骨分化能力明显更强。例如,在第 7 天,Ctrl-Exo 组的 OPN 基因表达量分别是空白组和 Exo-mBG 组的 3.97 倍和 2.83 倍。在颅骨缺损大鼠模型中,Exo-mBG 促进了骨组织愈合和血管生成,增加了 M2 巨噬细胞极化,抑制了 M1 巨噬细胞极化,这一点已通过显微 CT、H&E 染色、Masson 染色和免疫荧光染色得到验证。结论:这项研究为外泌体在无细胞疗法中的应用提供了启示,也为间充质干细胞外泌体在骨缺损修复中的应用提供了新的科学依据和技术方法。本文的转化潜力我们的研究表明,mBG刺激间充质干细胞产生的外泌体具有良好的体外和体内骨赋活和免疫调节功能,为外泌体在临床无细胞疗法中的应用提供了启示。
{"title":"Mesoporous bioactive glass-enhanced MSC-derived exosomes promote bone regeneration and immunomodulation in vitro and in vivo","authors":"Qingde Wa ,&nbsp;Yongxiang Luo ,&nbsp;Yubo Tang ,&nbsp;Jiaxiang Song ,&nbsp;Penghui Zhang ,&nbsp;Xitao Linghu ,&nbsp;Sien Lin ,&nbsp;Gang Li ,&nbsp;Yixiao Wang ,&nbsp;Zhenyu Wen ,&nbsp;Shuai Huang ,&nbsp;Weikang Xu","doi":"10.1016/j.jot.2024.09.009","DOIUrl":"10.1016/j.jot.2024.09.009","url":null,"abstract":"<div><h3>Background</h3><div>Exosomes produced by mesenchymal stem cells (MSCs) have vascular generative properties and are considered new effective candidates for the treatment of bone defects as alternatives to cell therapy. Improving the pro-regenerative function and efficacy of exosomes has been a popular research topic in the field of orthopaedics.</div></div><div><h3>Methods</h3><div>We prepared mesoporous bioactive glass (mBG) microspheres via the template method. The ionic products of mBGs used to treat MSCs were extracted, and the effects of exosomes secreted by MSCs on osteoblast (OB) and macrophage (MP) behaviour and bone defect repair were observed in vivo (Micro-CT, H&amp;E, Masson, and immunofluorescence staining for BMP2, COL1, VEGF, CD31, CD163, and iNOS).</div></div><div><h3>Results</h3><div>The mBG spheres were successfully prepared, and the Exo-mBG were isolated and extracted. Compared with those in the blank and Exo-Con groups, the proliferation and osteogenic differentiation of OBs in the Exo-mBG group were significantly greater. For example, on Day 7, OPN gene expression in the Ctrl-Exo group was 3.97 and 2.83 times greater than that in the blank and Exo-mBG groups, respectively. In a cranial defect rat model, Exo-mBG promoted bone tissue healing and angiogenesis, increased M2 macrophage polarisation and inhibited M1 macrophage polarisation, as verified by micro-CT, H&amp;E staining, Masson staining and immunofluorescence staining. These effects may be due to the combination of a higher silicon concentration and a higher calcium-to-phosphorus ratio in the mBG ionic products.</div></div><div><h3>Conclusion</h3><div>This study provides insights for the application of exosomes in cell-free therapy and a new scientific basis and technical approach for the utilisation of MSC-derived exosomes in bone defect repair.</div></div><div><h3>The translational potential of this article</h3><div>Our study demonstrated that exosomes produced by mBG-stimulated MSCs have excellent in vitro and in vivo bone-enabling and immunomodulatory functions and provides insights into the use of exosomes in clinical cell-free therapies.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"49 ","pages":"Pages 264-282"},"PeriodicalIF":5.9,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142539564","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}
引用次数: 0
Engineered melatonin-pretreated plasma exosomes repair traumatic spinal cord injury by regulating miR-138-5p/SOX4 axis mediated microglia polarization 经褪黑素预处理的工程血浆外泌体通过调节 miR-138-5p/SOX4 轴介导的小胶质细胞极化修复创伤性脊髓损伤
IF 5.9 1区 医学 Q1 ORTHOPEDICS Pub Date : 2024-10-24 DOI: 10.1016/j.jot.2024.09.007
Hao Chen , Huihui Sun , Yaqing Yang , Pingchuan Wang , Xizhao Chen , Junxiang Yin , Aoying Li , Liang Zhang , Jun Cai , Jijun Huang , Shengfei Zhang , Zhiqiang Zhang , Xinmin Feng , Jian Yin , Yongxiang Wang , Wu Xiong , Bowen Wan

Background

Neuroinflammation plays a crucial role in the repair of spinal cord injury (SCI), with microglia, pivotal in neuroinflammation, driving either degeneration or recovery in this pathological process. Recently, plasma-derived exosomes (denoted Exos) have presented a high capacity for promoting functional recovery of SCI through the anti-inflammatory effects, and pretreated exosomes are associated with better outcomes. Thus, we aimed to explore whether melatonin-pretreated plasma-derived exosomes (denoted MExo) could exert superior effects on SCI, and attempted to elucidate the potential mechanisms.

Methods

Electron microscopy, nanoparticle tracking analysis, and western blot were applied to delineate the distinctions between Exos and MExos. To assess their therapeutic potentials, we established a contusion SCI rat model, complemented by a battery of in vitro experiments comparing both groups. Subsequently, a miRNA microarray analysis was conducted, followed by a series of rescue experiments to elucidate the specific role of miRNAs in MExos. To further delve into the molecular mechanisms involved, we employed western blot analysis and the luciferase reporter gene assay.

Results

Melatonin promoted the release of exosome from plasma, concurrently amplifying their anti-inflammatory properties. Furthermore, it was discerned that MExos facilitated a transition in microglia polarization from M1 to M2 phenotype, a phenomenon more pronounced than that observed with Exos. In an endeavor to elucidate this variance, we scrutinized miRNAs exhibiting elevated expression levels in MExos, pinpointing miR-138-5p as a pivotal element in this dynamic. Following this, an in-depth investigation into the role of miR-138-5p was undertaken, which uncovered its efficacy in driving phenotypic alterations within microglia. The analysis of downstream genes targeted by miR-138-5p revealed that it exerted a negative regulatory influence on SOX4, which was found to obstruct the generation of M2-type microglia and the secretion of anti-inflammatory cytokines, thereby partially elucidating the mechanism behind miR-138-5p′s regulation of microglia polarization.

Conclusions

We innovatively observed that melatonin enhanced the anti-inflammatory function of Exos, which further decreased the expression of SOX4 by delivering miR-138-5p. This inhibition promoted the conversion of M1 microglia to M2 microglia, thus offering a viable option for the treatment of SCI.

The translational potential of this article

This study highlights that melatonin enhances the anti-inflammatory function of Exos through delivery of miR-138-5p. Activation of miR-138-5p/SOX4 axis by engineered melatonin-pretreated plasma exosomes may be a potential target for SCI treatment.
背景神经炎症在脊髓损伤(SCI)的修复过程中起着至关重要的作用,而小胶质细胞在神经炎症中起着关键作用,它们在这一病理过程中推动着脊髓损伤的退化或恢复。最近,血浆衍生的外泌体(Exos)通过抗炎作用促进了脊髓损伤的功能恢复,预处理的外泌体与更好的预后相关。因此,我们旨在探索褪黑素预处理的血浆衍生外泌体(MExo)是否能对 SCI 发挥更好的作用,并试图阐明其潜在机制。为了评估它们的治疗潜力,我们建立了一个挫伤 SCI 大鼠模型,并通过一系列体外实验对两组模型进行了比较。随后,我们进行了 miRNA 微阵列分析,并进行了一系列挽救实验,以阐明 miRNA 在 MExos 中的特殊作用。为了进一步深入研究其中的分子机制,我们采用了 Western 印迹分析和荧光素酶报告基因实验。结果褪黑素促进了血浆中外泌体的释放,同时增强了其抗炎特性。此外,研究还发现,MExos 促进了小胶质细胞极化从 M1 型向 M2 型的转变,这一现象比 Exos 更为明显。为了阐明这种差异,我们仔细研究了在 MExos 中表达水平升高的 miRNA,发现 miR-138-5p 是这种动态变化的关键因素。随后,我们对 miR-138-5p 的作用进行了深入研究,发现了它在驱动小胶质细胞表型改变方面的功效。对 miR-138-5p 靶向的下游基因的分析表明,它对 SOX4 起着负向调控作用,而 SOX4 则阻碍了 M2 型小胶质细胞的生成和抗炎细胞因子的分泌,从而部分阐明了 miR-138-5p 对小胶质细胞极化的调控机制。结论我们创新性地观察到,褪黑激素增强了 Exos 的抗炎功能,而 Exos 通过传递 miR-138-5p 进一步降低了 SOX4 的表达。这种抑制作用促进了 M1 小胶质细胞向 M2 小胶质细胞的转化,从而为治疗 SCI 提供了一种可行的选择。经褪黑素预处理的工程血浆外泌体可激活miR-138-5p/SOX4轴,这可能是治疗SCI的一个潜在靶点。
{"title":"Engineered melatonin-pretreated plasma exosomes repair traumatic spinal cord injury by regulating miR-138-5p/SOX4 axis mediated microglia polarization","authors":"Hao Chen ,&nbsp;Huihui Sun ,&nbsp;Yaqing Yang ,&nbsp;Pingchuan Wang ,&nbsp;Xizhao Chen ,&nbsp;Junxiang Yin ,&nbsp;Aoying Li ,&nbsp;Liang Zhang ,&nbsp;Jun Cai ,&nbsp;Jijun Huang ,&nbsp;Shengfei Zhang ,&nbsp;Zhiqiang Zhang ,&nbsp;Xinmin Feng ,&nbsp;Jian Yin ,&nbsp;Yongxiang Wang ,&nbsp;Wu Xiong ,&nbsp;Bowen Wan","doi":"10.1016/j.jot.2024.09.007","DOIUrl":"10.1016/j.jot.2024.09.007","url":null,"abstract":"<div><h3>Background</h3><div>Neuroinflammation plays a crucial role in the repair of spinal cord injury (SCI), with microglia, pivotal in neuroinflammation, driving either degeneration or recovery in this pathological process. Recently, plasma-derived exosomes (denoted Exos) have presented a high capacity for promoting functional recovery of SCI through the anti-inflammatory effects, and pretreated exosomes are associated with better outcomes. Thus, we aimed to explore whether melatonin-pretreated plasma-derived exosomes (denoted MExo) could exert superior effects on SCI, and attempted to elucidate the potential mechanisms.</div></div><div><h3>Methods</h3><div>Electron microscopy, nanoparticle tracking analysis, and western blot were applied to delineate the distinctions between Exos and MExos. To assess their therapeutic potentials, we established a contusion SCI rat model, complemented by a battery of in vitro experiments comparing both groups. Subsequently, a miRNA microarray analysis was conducted, followed by a series of rescue experiments to elucidate the specific role of miRNAs in MExos. To further delve into the molecular mechanisms involved, we employed western blot analysis and the luciferase reporter gene assay.</div></div><div><h3>Results</h3><div>Melatonin promoted the release of exosome from plasma, concurrently amplifying their anti-inflammatory properties. Furthermore, it was discerned that MExos facilitated a transition in microglia polarization from M1 to M2 phenotype, a phenomenon more pronounced than that observed with Exos. In an endeavor to elucidate this variance, we scrutinized miRNAs exhibiting elevated expression levels in MExos, pinpointing miR-138-5p as a pivotal element in this dynamic. Following this, an in-depth investigation into the role of miR-138-5p was undertaken, which uncovered its efficacy in driving phenotypic alterations within microglia. The analysis of downstream genes targeted by miR-138-5p revealed that it exerted a negative regulatory influence on SOX4, which was found to obstruct the generation of M2-type microglia and the secretion of anti-inflammatory cytokines, thereby partially elucidating the mechanism behind miR-138-5p′s regulation of microglia polarization.</div></div><div><h3>Conclusions</h3><div>We innovatively observed that melatonin enhanced the anti-inflammatory function of Exos, which further decreased the expression of SOX4 by delivering miR-138-5p. This inhibition promoted the conversion of M1 microglia to M2 microglia, thus offering a viable option for the treatment of SCI.</div></div><div><h3>The translational potential of this article</h3><div>This study highlights that melatonin enhances the anti-inflammatory function of Exos through delivery of miR-138-5p. Activation of miR-138-5p/SOX4 axis by engineered melatonin-pretreated plasma exosomes may be a potential target for SCI treatment.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"49 ","pages":"Pages 230-245"},"PeriodicalIF":5.9,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142526265","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}
引用次数: 0
Engineering natural DNA matrices with halloysite nanotubes to fabricate injectable therapeutic hydrogels for bone regeneration 用哈洛来石纳米管改造天然 DNA 基质,制造用于骨再生的可注射治疗水凝胶
IF 5.9 1区 医学 Q1 ORTHOPEDICS Pub Date : 2024-10-22 DOI: 10.1016/j.jot.2024.09.010
Yali Miao , Teliang Lu , Shangbin Cui , Ziyang Xu , Xiao Liu , Yu Zhang

Background

Injectable hydrogels are widely used in drug delivery and the repair of irregular tissue defects due to their advantages such as convenient and minimally invasive operation. Although the existing injectable hydrogels have excellent biocompatibility and osteoconduction, they still face clinical challenges such as low osteogenic activity. The key requirements for improved injectable hydrogels as repair materials for non-load bearing bone defects are optimal handling properties, the ability to fill irregular defects and provide osteoinductive stimulation.

Methods

We developed an approach to construct injectable hydrogels through a two-step gelation process. In the first step of gelation, the denaturation and rehybridization mechanism of natural biopolymer DNA was utilized to form interconnected structure through hydrogen bonding between complementary base pairs between the DNA strands. In the second step of gelation, the introduction of halloysite nanotubes (HNTs) loaded with osteogenic model drug dexamethasone (Dex) provided additional crosslinking sites through non-covalent interactions with the DNA backbone, including electrostatic interaction and hydrogen bonding interaction.

Results

The DNA-based nanocomposite hydrogel material developed in our work can be used as an injectable filling material for the repair of non-load bearing bone defect and can be loaded with osteogenic model drug dexamethasone (Dex) for improved osteoinductivity, promoting new bone regeneration in vivo.

Translational potential of this article

This article highlights the potential of using nanocomposite hydrogels to repair non-load bearing bone defects, which are common injuries in the clinic. This study provides a deeper understanding of how to optimize the properties of hydrogels to regulate cell differentiation and tissue formation.
背景可注射水凝胶因其操作方便、微创等优点被广泛应用于药物输送和不规则组织缺损的修复。虽然现有的可注射水凝胶具有良好的生物相容性和骨传导性,但它们仍然面临着成骨活性低等临床挑战。改良可注射水凝胶作为非承重骨缺损修复材料的关键要求是具有最佳的操作性能、填充不规则缺损的能力以及提供骨诱导刺激。在凝胶化的第一步,利用天然生物聚合物 DNA 的变性和再杂化机制,通过 DNA 链之间互补碱基对的氢键作用形成相互连接的结构。在凝胶化的第二步,加入了成骨模型药物地塞米松(Dex)的海泡石纳米管(HNTs)通过与 DNA 主干的非共价相互作用(包括静电作用和氢键作用)提供了额外的交联位点。结果我们工作中开发的基于DNA的纳米复合水凝胶材料可用作修复非承重骨缺损的注射填充材料,并可负载成骨模型药物地塞米松(Dex)以改善骨诱导性,促进体内新骨再生。这项研究加深了人们对如何优化水凝胶特性以调节细胞分化和组织形成的理解。
{"title":"Engineering natural DNA matrices with halloysite nanotubes to fabricate injectable therapeutic hydrogels for bone regeneration","authors":"Yali Miao ,&nbsp;Teliang Lu ,&nbsp;Shangbin Cui ,&nbsp;Ziyang Xu ,&nbsp;Xiao Liu ,&nbsp;Yu Zhang","doi":"10.1016/j.jot.2024.09.010","DOIUrl":"10.1016/j.jot.2024.09.010","url":null,"abstract":"<div><h3>Background</h3><div>Injectable hydrogels are widely used in drug delivery and the repair of irregular tissue defects due to their advantages such as convenient and minimally invasive operation. Although the existing injectable hydrogels have excellent biocompatibility and osteoconduction, they still face clinical challenges such as low osteogenic activity. The key requirements for improved injectable hydrogels as repair materials for non-load bearing bone defects are optimal handling properties, the ability to fill irregular defects and provide osteoinductive stimulation.</div></div><div><h3>Methods</h3><div>We developed an approach to construct injectable hydrogels through a two-step gelation process. In the first step of gelation, the denaturation and rehybridization mechanism of natural biopolymer DNA was utilized to form interconnected structure through hydrogen bonding between complementary base pairs between the DNA strands. In the second step of gelation, the introduction of halloysite nanotubes (HNTs) loaded with osteogenic model drug dexamethasone (Dex) provided additional crosslinking sites through non-covalent interactions with the DNA backbone, including electrostatic interaction and hydrogen bonding interaction.</div></div><div><h3>Results</h3><div>The DNA-based nanocomposite hydrogel material developed in our work can be used as an injectable filling material for the repair of non-load bearing bone defect and can be loaded with osteogenic model drug dexamethasone (Dex) for improved osteoinductivity, promoting new bone regeneration <em>in vivo</em>.</div></div><div><h3>Translational potential of this article</h3><div>This article highlights the potential of using nanocomposite hydrogels to repair non-load bearing bone defects, which are common injuries in the clinic. This study provides a deeper understanding of how to optimize the properties of hydrogels to regulate cell differentiation and tissue formation.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"49 ","pages":"Pages 218-229"},"PeriodicalIF":5.9,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142526264","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}
引用次数: 0
IHH–GLI-1–HIF-2α signalling influences hypertrophic chondrocytes to exacerbate osteoarthritis progression IHH-GLI-1-HIF-2α信号影响肥大软骨细胞,加剧骨关节炎进展
IF 5.9 1区 医学 Q1 ORTHOPEDICS Pub Date : 2024-10-22 DOI: 10.1016/j.jot.2024.09.008
Chengming Zhang , Ruipeng Zhao , Zhengquan Dong , Yang Liu , Mengrou Liu , Haoqian Li , Yukun Yin , Xianda Che , Gaige Wu , li Guo , Pengcui Li , Xiaochun Wei , Ziquan Yang
<div><h3>Background</h3><div>Chondrocyte hypertrophy is a potential target for osteoarthritis (OA) treatment, with Indian hedgehog (IHH), glioma-associated oncogene homolog (GLI), and hypoxia-inducible factor-2α (HIF-2α) being closely associated with chondrocyte hypertrophy during OA progression. Whereas IHH can modulate chondrocyte hypertrophy, interference with IHH signalling has not achieved the anticipated therapeutic effects and poses safety concerns, necessitating further clarification of the specific mechanisms by which IHH affects articular cartilage degeneration. Inhibition of the HIF-2α overexpression in cartilage slows the progression of early OA, but the mechanisms underlying HIF-2α accumulation in OA cartilage remain unclear. The aim of this study was to determine the function of Ihh, as well as its downstream factors, in chondrocytes, based on an early osteoarthritis (OA) mouse model and in vitro chondrocyte model.</div></div><div><h3>Methods</h3><div>Investigated the expression levels and locations of IHH–GLI-1 pathway in normal and early degenerated human cartilage, comparing them with HIF-2α and its downstream factors. RT-qPCR, Western blotting, Crystal violet staining, and EdU assays were used to evaluate the pecific regulatory mechanisms of the IHH–GLI-1–HIF-2α signalling axis in normal chondrocytes and in chondrocytes under inflammatory conditions. Validated the impact of IHH on early cartilage degeneration and the relationship between the IHH-GLI-1 pathway and the expression levels and expression locations of HIF-2α and its downstream factors in Col2a1-Cre<sup>ERT2</sup>;Ihh<sup>fl/fl</sup> mice.</div></div><div><h3>Results</h3><div>In early-stage degenerative joint cartilage, the GLI-1 pathway in hypertrophic chondrocytes exhibited similar changes in location and levels to HIF-2α and its downstream factor vascular endothelial growth factor (VEGF). In vitro, IHH–GLI-1–HIF-2α signalling activation in chondrocytes under physiological hypoxic conditions inhibited chondrocyte proliferation. In chondrocytes stimulated by inflammatory environments, IHH inhibited the degradation of HIF-2α via the GLI-1 pathway, thereby promoting HIF-2α protein expression. Elevated HIF-2α expression further enhanced intracellular IHH–GLI-1 levels, generating a positive feedback loop to collectively regulate the expression of downstream hypertrophic factors and matrix-degradation factors. <em>In vivo</em>, conditional <em>Ihh</em> knockout in mouse chondrocytes downregulated Hif-2α protein expression in early degenerative cartilage tissue and affected the expression of downstream Vegf and hypertrophic factors.</div></div><div><h3>Conclusions</h3><div>During OA progression, the IHH–GLI-1–HIF-2α axis mainly operates within hypertrophic chondrocytes, exacerbating cartilage degeneration by regulating hypertrophic chondrocyte functions, cartilage matrix degradation, and microvascular invasion.</div></div><div><h3>The translational potential of this article
背景软骨细胞肥大是骨关节炎(OA)治疗的一个潜在靶点,印度刺猬(IHH)、胶质瘤相关癌基因同源物(GLI)和缺氧诱导因子-2α(HIF-2α)与OA进展过程中的软骨细胞肥大密切相关。虽然 IHH 可以调节软骨细胞肥大,但干扰 IHH 信号并不能达到预期的治疗效果,而且还存在安全隐患,因此有必要进一步阐明 IHH 影响关节软骨退化的具体机制。抑制软骨中HIF-2α的过度表达可减缓早期OA的进展,但HIF-2α在OA软骨中积累的机制仍不清楚。本研究的目的是基于早期骨关节炎(OA)小鼠模型和体外软骨细胞模型,确定 Ihh 及其下游因子在软骨细胞中的功能。方法研究 IHH-GLI-1 通路在正常和早期退化人类软骨中的表达水平和位置,并与 HIF-2α 及其下游因子进行比较。通过 RT-qPCR、Western 印迹、水晶紫染色和 EdU 检测,评估了 IHH-GLI-1-HIF-2α 信号轴在正常软骨细胞和炎症条件下软骨细胞中的特殊调控机制。验证了 IHH 对早期软骨退化的影响,以及 IHH-GLI-1 通路与 Col2a1-CreERT2;Ihhfl/fl 小鼠中 HIF-2α 及其下游因子的表达水平和表达位置之间的关系。在体外,生理缺氧条件下软骨细胞中的 IHH-GLI-1-HIF-2α 信号激活会抑制软骨细胞的增殖。在受到炎症环境刺激的软骨细胞中,IHH 通过 GLI-1 通路抑制了 HIF-2α 的降解,从而促进了 HIF-2α 蛋白的表达。HIF-2α表达的升高进一步提高了细胞内IHH-GLI-1的水平,形成了一个正反馈回路,共同调节下游肥大因子和基质降解因子的表达。在体内,小鼠软骨细胞中条件性 Ihh 基因敲除可下调早期退行性软骨组织中 Hif-2α 蛋白的表达,并影响下游 Vegf 和肥大因子的表达。结论在OA进展过程中,IHH-GLI-1-HIF-2α轴主要在肥大软骨细胞内发挥作用,通过调控肥大软骨细胞功能、软骨基质降解和微血管侵袭加剧软骨退行性变。
{"title":"IHH–GLI-1–HIF-2α signalling influences hypertrophic chondrocytes to exacerbate osteoarthritis progression","authors":"Chengming Zhang ,&nbsp;Ruipeng Zhao ,&nbsp;Zhengquan Dong ,&nbsp;Yang Liu ,&nbsp;Mengrou Liu ,&nbsp;Haoqian Li ,&nbsp;Yukun Yin ,&nbsp;Xianda Che ,&nbsp;Gaige Wu ,&nbsp;li Guo ,&nbsp;Pengcui Li ,&nbsp;Xiaochun Wei ,&nbsp;Ziquan Yang","doi":"10.1016/j.jot.2024.09.008","DOIUrl":"10.1016/j.jot.2024.09.008","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Chondrocyte hypertrophy is a potential target for osteoarthritis (OA) treatment, with Indian hedgehog (IHH), glioma-associated oncogene homolog (GLI), and hypoxia-inducible factor-2α (HIF-2α) being closely associated with chondrocyte hypertrophy during OA progression. Whereas IHH can modulate chondrocyte hypertrophy, interference with IHH signalling has not achieved the anticipated therapeutic effects and poses safety concerns, necessitating further clarification of the specific mechanisms by which IHH affects articular cartilage degeneration. Inhibition of the HIF-2α overexpression in cartilage slows the progression of early OA, but the mechanisms underlying HIF-2α accumulation in OA cartilage remain unclear. The aim of this study was to determine the function of Ihh, as well as its downstream factors, in chondrocytes, based on an early osteoarthritis (OA) mouse model and in vitro chondrocyte model.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Investigated the expression levels and locations of IHH–GLI-1 pathway in normal and early degenerated human cartilage, comparing them with HIF-2α and its downstream factors. RT-qPCR, Western blotting, Crystal violet staining, and EdU assays were used to evaluate the pecific regulatory mechanisms of the IHH–GLI-1–HIF-2α signalling axis in normal chondrocytes and in chondrocytes under inflammatory conditions. Validated the impact of IHH on early cartilage degeneration and the relationship between the IHH-GLI-1 pathway and the expression levels and expression locations of HIF-2α and its downstream factors in Col2a1-Cre&lt;sup&gt;ERT2&lt;/sup&gt;;Ihh&lt;sup&gt;fl/fl&lt;/sup&gt; mice.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;In early-stage degenerative joint cartilage, the GLI-1 pathway in hypertrophic chondrocytes exhibited similar changes in location and levels to HIF-2α and its downstream factor vascular endothelial growth factor (VEGF). In vitro, IHH–GLI-1–HIF-2α signalling activation in chondrocytes under physiological hypoxic conditions inhibited chondrocyte proliferation. In chondrocytes stimulated by inflammatory environments, IHH inhibited the degradation of HIF-2α via the GLI-1 pathway, thereby promoting HIF-2α protein expression. Elevated HIF-2α expression further enhanced intracellular IHH–GLI-1 levels, generating a positive feedback loop to collectively regulate the expression of downstream hypertrophic factors and matrix-degradation factors. &lt;em&gt;In vivo&lt;/em&gt;, conditional &lt;em&gt;Ihh&lt;/em&gt; knockout in mouse chondrocytes downregulated Hif-2α protein expression in early degenerative cartilage tissue and affected the expression of downstream Vegf and hypertrophic factors.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;During OA progression, the IHH–GLI-1–HIF-2α axis mainly operates within hypertrophic chondrocytes, exacerbating cartilage degeneration by regulating hypertrophic chondrocyte functions, cartilage matrix degradation, and microvascular invasion.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;The translational potential of this article","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"49 ","pages":"Pages 207-217"},"PeriodicalIF":5.9,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142526263","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}
引用次数: 0
期刊
Journal of Orthopaedic Translation
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1