Pub Date : 2025-01-01DOI: 10.1016/j.jot.2024.10.007
Fuchou Hsiang , Yun Gao , Yiyang Ma , Peichun Hsu , Cheng Qiu , Kaiwen Zheng , Yidan Pang , Jinyu Zhu , Weibin Yu , Chun Chen , Changqing Zhang , Dajiang Du
<div><h3>Background</h3><div>Mosaic transplantation using autologous osteochondral graft (AOCG) is an effective treatment for osteochondral lesion however, at the sacrifice of irreversible damage to the donor articular surface. Costal cartilage is hyaline cartilage and has been utilized as a donor source in various surgeries. This study investigates the use of autologous costal cartilage graft (ACCG) for treating femoral head osteochondral defects in a swine model.</div></div><div><h3>Methods</h3><div>Osteochondral defects were surgically induced in the femoral heads of one-year-old Bama pigs regardless of sex. The swine were divided into a Defect group without grafting (n = 6), a group grafted with ACCG (n = 6) and a group grafted with AOCG from ipsilateral trochlear groove (n = 6). Postoperatively, swine were allowed free cage activity without immobilization and were euthanized at either 3 or 6 months. Repair effects were evaluated using μCT, MRI, histology and immunohistochemistry (IHC) to assess the osteochondral properties of the grafted femoral head.</div></div><div><h3>Results</h3><div>There was no difference in the hip function of the Bama pigs between AOCG and ACCG groups. The International Cartilage Repair Society (ICRS) scores showed no difference between AOCG and ACCG at both time points. ACCG exhibited comparable trabecular thickness as AOCG's, but lower trabecular number and higher trabecular separation. Percent bone volume was significantly lower in the ACCG group when compared to AOCG at 3 months, but not at 6 months. Modified MOCART scores were significantly higher in the AOCG group at 3 months but not at 6 months. MRI also detected increasing degree of ossification in the costal cartilage graft at all time points. Histologically, ACCG formed a subchondral bone interface while maintaining the hyaline cartilage characteristics on the articular surface. We also found that superficial layer of ACCG integrated more thoroughly with the recipient cartilage than AOCG did. Furthermore, histology and IHC collectively demonstrated that ACCG had undergone endochondral ossification process at the subchondral layer, evidenced by increased type I collagen expression and decreased type II collagen expression. No donor-site morbidity was noted with ACCG procedure during the study.</div></div><div><h3>Conclusions</h3><div>This study demonstrates that ACCG can serve as a viable alternative to AOCG for treating femoral head osteochondral defects. The findings show that ACCG offers comparable outcomes to AOCG while avoiding the donor-site morbidity associated with AOCG. Given the challenges related to the donor tissue availability and associated complications in the clinical practice, ACCG could provide a promising and less invasive option for cartilage repair.</div></div><div><h3>The translational potential of this article</h3><div>This proposed method can be translated into practical treatment for repairing osteochondral lesion in human hip joints
{"title":"Repair of the femoral head osteochondral defect in a swine model using autologous costal cartilage graft transplantation","authors":"Fuchou Hsiang , Yun Gao , Yiyang Ma , Peichun Hsu , Cheng Qiu , Kaiwen Zheng , Yidan Pang , Jinyu Zhu , Weibin Yu , Chun Chen , Changqing Zhang , Dajiang Du","doi":"10.1016/j.jot.2024.10.007","DOIUrl":"10.1016/j.jot.2024.10.007","url":null,"abstract":"<div><h3>Background</h3><div>Mosaic transplantation using autologous osteochondral graft (AOCG) is an effective treatment for osteochondral lesion however, at the sacrifice of irreversible damage to the donor articular surface. Costal cartilage is hyaline cartilage and has been utilized as a donor source in various surgeries. This study investigates the use of autologous costal cartilage graft (ACCG) for treating femoral head osteochondral defects in a swine model.</div></div><div><h3>Methods</h3><div>Osteochondral defects were surgically induced in the femoral heads of one-year-old Bama pigs regardless of sex. The swine were divided into a Defect group without grafting (n = 6), a group grafted with ACCG (n = 6) and a group grafted with AOCG from ipsilateral trochlear groove (n = 6). Postoperatively, swine were allowed free cage activity without immobilization and were euthanized at either 3 or 6 months. Repair effects were evaluated using μCT, MRI, histology and immunohistochemistry (IHC) to assess the osteochondral properties of the grafted femoral head.</div></div><div><h3>Results</h3><div>There was no difference in the hip function of the Bama pigs between AOCG and ACCG groups. The International Cartilage Repair Society (ICRS) scores showed no difference between AOCG and ACCG at both time points. ACCG exhibited comparable trabecular thickness as AOCG's, but lower trabecular number and higher trabecular separation. Percent bone volume was significantly lower in the ACCG group when compared to AOCG at 3 months, but not at 6 months. Modified MOCART scores were significantly higher in the AOCG group at 3 months but not at 6 months. MRI also detected increasing degree of ossification in the costal cartilage graft at all time points. Histologically, ACCG formed a subchondral bone interface while maintaining the hyaline cartilage characteristics on the articular surface. We also found that superficial layer of ACCG integrated more thoroughly with the recipient cartilage than AOCG did. Furthermore, histology and IHC collectively demonstrated that ACCG had undergone endochondral ossification process at the subchondral layer, evidenced by increased type I collagen expression and decreased type II collagen expression. No donor-site morbidity was noted with ACCG procedure during the study.</div></div><div><h3>Conclusions</h3><div>This study demonstrates that ACCG can serve as a viable alternative to AOCG for treating femoral head osteochondral defects. The findings show that ACCG offers comparable outcomes to AOCG while avoiding the donor-site morbidity associated with AOCG. Given the challenges related to the donor tissue availability and associated complications in the clinical practice, ACCG could provide a promising and less invasive option for cartilage repair.</div></div><div><h3>The translational potential of this article</h3><div>This proposed method can be translated into practical treatment for repairing osteochondral lesion in human hip joints","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"50 ","pages":"Pages 413-422"},"PeriodicalIF":5.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143600499","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 : 2025-01-01DOI: 10.1016/j.jot.2024.12.002
Daxue Zhu , Zhaoheng Wang , Yanhu Li , Shijie Chen , Xuewen Kang
Background
Intervertebral disc degeneration (IDD) is a prevalent etiology of low back pain in the global adult population, leading to considerable morbidity and healthcare costs. Existing therapeutic modalities for IDD remain constrained. Ferroptosis in the nucleus pulposus (NP) cells emerges as a pivotal contributor to IDD. Humanin (HN), a mitochondrial-secreted peptide, is intricately linked to age-related maladies and showcases antioxidant, anti-inflammatory, and anti-apoptotic properties. Nonetheless, its precise involvement in IDD remains enigmatic.
Methods
The expression profile of HN in IDD was scrutinized utilizing human NP cell cultures and an IDD rat model (n = 5). The therapeutic efficacy of HN in rats was assessed via MRI and histological evaluation, alongside an exploration of the molecular underpinnings of HN's therapeutic actions in IDD management.
Results
This pioneering study unveiled a downregulation of HN expression in IDD patients, a finding corroborated through cell and rat IDD models. Furthermore, it was ascertained that exogenous HN could trigger endogenous HN expression, impede the JAK2/STAT3 and NF-κB pathways, thereby mitigating erastin-induced ferroptosis in NP cells, contingent upon the upregulation of HSP27 expression. Moreover, the study validated the role of HN in preserving mitochondrial homeostasis, curbing mitochondrial reactive oxygen species (mtROS) generation and mtDNA leakage, consequently hindering mtDNA binding to TLR9 and subsequent activation of the NF-κB pathway. Notably, in vivo rat experiments underscored the efficacy of HN treatment in ameliorating IDD progression induced by annulus fibrosus puncture.
Conclusion
By assuaging ferroptosis in NP cells, HN exhibits promise as a viable candidate for IDD treatment, capable of impeding disease advancement. The translational potential of this article: This study highlights the importance and effectiveness of HN in alleviating IDD by inhibiting ferroptosis in NP cells. The addition of exogenous HN may represent a potential therapeutic strategy for treating IDD.
{"title":"Humanin reduces nucleus pulposus cells ferroptosis to alleviate intervertebral disc degeneration: An in vitro and in vivo study","authors":"Daxue Zhu , Zhaoheng Wang , Yanhu Li , Shijie Chen , Xuewen Kang","doi":"10.1016/j.jot.2024.12.002","DOIUrl":"10.1016/j.jot.2024.12.002","url":null,"abstract":"<div><h3>Background</h3><div>Intervertebral disc degeneration (IDD) is a prevalent etiology of low back pain in the global adult population, leading to considerable morbidity and healthcare costs. Existing therapeutic modalities for IDD remain constrained. Ferroptosis in the nucleus pulposus (NP) cells emerges as a pivotal contributor to IDD. Humanin (HN), a mitochondrial-secreted peptide, is intricately linked to age-related maladies and showcases antioxidant, anti-inflammatory, and anti-apoptotic properties. Nonetheless, its precise involvement in IDD remains enigmatic.</div></div><div><h3>Methods</h3><div>The expression profile of HN in IDD was scrutinized utilizing human NP cell cultures and an IDD rat model (n = 5). The therapeutic efficacy of HN in rats was assessed via MRI and histological evaluation, alongside an exploration of the molecular underpinnings of HN's therapeutic actions in IDD management.</div></div><div><h3>Results</h3><div>This pioneering study unveiled a downregulation of HN expression in IDD patients, a finding corroborated through cell and rat IDD models. Furthermore, it was ascertained that exogenous HN could trigger endogenous HN expression, impede the JAK2/STAT3 and NF-κB pathways, thereby mitigating erastin-induced ferroptosis in NP cells, contingent upon the upregulation of HSP27 expression. Moreover, the study validated the role of HN in preserving mitochondrial homeostasis, curbing mitochondrial reactive oxygen species (mtROS) generation and mtDNA leakage, consequently hindering mtDNA binding to TLR9 and subsequent activation of the NF-κB pathway. Notably, in vivo rat experiments underscored the efficacy of HN treatment in ameliorating IDD progression induced by annulus fibrosus puncture.</div></div><div><h3>Conclusion</h3><div>By assuaging ferroptosis in NP cells, HN exhibits promise as a viable candidate for IDD treatment, capable of impeding disease advancement. <strong>The translational potential of this article</strong>: This study highlights the importance and effectiveness of HN in alleviating IDD by inhibiting ferroptosis in NP cells. The addition of exogenous HN may represent a potential therapeutic strategy for treating IDD.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"50 ","pages":"Pages 274-294"},"PeriodicalIF":5.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11788685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122909","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 : 2025-01-01DOI: 10.1016/j.jot.2024.10.002
Rou Li , Shiqing Xu , Yanning Guo , Cong Cao , Jingchen Xu , Lijun Hao , Sai Luo , Xinyao Chen , Yuyang Du , Ye Li , Yong Xie , Weitong Gao , Jing Li , Baohua Xu
At present, there is a significant population of individuals experiencing bone deficiencies caused by injuries, ailments affecting the bones, congenital abnormalities, and cancer. The management of substantial bone defects a significant global orthopedic challenge due to the intricacies involved in promoting and restoring the growth of fresh osseous tissue. Autografts are widely regarded as the “gold standard” for repairing bone defects because of their superior tissue acceptance and ability to control osteogenesis. However, patients undergoing autografts may encounter various challenges, including but not limited to hernia, bleeding, nerve impairment, tissue death. Therefore, researchers in regenerative medicine are striving to find alternatives. Collagen is the most abundant protein in the human body, and its triple helix structure gives it unique characteristics that contribute to its strength and functionality in various tissues. Collagen is commonly processed into various forms such as scaffolds, sponges, membranes, hydrogels, and composite materials, due to its unique compatibility with the human body, affinity for water, minimal potential for immune reactions, adaptability, and ability to transport nutrients or drugs. As an alternative material in the field of bone regeneration, collagen is becoming increasingly important. The objective of this review is to provide a comprehensive analysis of the primary types and sources of collagen, their processes of synthesis and degradation, as well as the advancements made in bone regeneration research and its potential applications. A comprehensive investigation into the role of collagen in bone regeneration is undertaken, providing valuable points of reference for a more profound comprehension of collagen applications in this field. The concluding section provides a comprehensive overview of the prospective avenues for collagen research, underscoring their promising future and highlighting their significant potential in the field of bone regeneration.
The Translational Potential of this Article. The comprehensive exploration into the diverse functions and translational potential of collagen in bone regeneration, as demonstrated in this review, these findings underscore their promising potential as a treatment option with significant clinical implications, thus paving the way for innovative and efficacious therapeutic strategies in this domain.
{"title":"Application of collagen in bone regeneration","authors":"Rou Li , Shiqing Xu , Yanning Guo , Cong Cao , Jingchen Xu , Lijun Hao , Sai Luo , Xinyao Chen , Yuyang Du , Ye Li , Yong Xie , Weitong Gao , Jing Li , Baohua Xu","doi":"10.1016/j.jot.2024.10.002","DOIUrl":"10.1016/j.jot.2024.10.002","url":null,"abstract":"<div><div>At present, there is a significant population of individuals experiencing bone deficiencies caused by injuries, ailments affecting the bones, congenital abnormalities, and cancer. The management of substantial bone defects a significant global orthopedic challenge due to the intricacies involved in promoting and restoring the growth of fresh osseous tissue. Autografts are widely regarded as the “gold standard” for repairing bone defects because of their superior tissue acceptance and ability to control osteogenesis. However, patients undergoing autografts may encounter various challenges, including but not limited to hernia, bleeding, nerve impairment, tissue death. Therefore, researchers in regenerative medicine are striving to find alternatives. Collagen is the most abundant protein in the human body, and its triple helix structure gives it unique characteristics that contribute to its strength and functionality in various tissues. Collagen is commonly processed into various forms such as scaffolds, sponges, membranes, hydrogels, and composite materials, due to its unique compatibility with the human body, affinity for water, minimal potential for immune reactions, adaptability, and ability to transport nutrients or drugs. As an alternative material in the field of bone regeneration, collagen is becoming increasingly important. The objective of this review is to provide a comprehensive analysis of the primary types and sources of collagen, their processes of synthesis and degradation, as well as the advancements made in bone regeneration research and its potential applications. A comprehensive investigation into the role of collagen in bone regeneration is undertaken, providing valuable points of reference for a more profound comprehension of collagen applications in this field. The concluding section provides a comprehensive overview of the prospective avenues for collagen research, underscoring their promising future and highlighting their significant potential in the field of bone regeneration.</div><div>The Translational Potential of this Article. The comprehensive exploration into the diverse functions and translational potential of collagen in bone regeneration, as demonstrated in this review, these findings underscore their promising potential as a treatment option with significant clinical implications, thus paving the way for innovative and efficacious therapeutic strategies in this domain.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"50 ","pages":"Pages 129-143"},"PeriodicalIF":5.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143177809","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 : 2025-01-01DOI: 10.1016/j.jot.2024.09.014
Shanfeng Chen , Yiming Dou , Yiming Zhang , Xun Sun , Xinyu Liu , Qiang Yang
Intervertebral disc degeneration is the leading cause of low back pain, imposing significant burdens on patients, societies, and economies. Advancements in regenerative medicine have spotlighted extracellular vesicles as promising nanoparticles for intervertebral disc degeneration treatment. Extracellular vesicles retain the potential of cell therapy and serve as carriers to deliver their cargo to target cells, thereby regulating cell activity. This review summarizes the biogenesis and molecular composition of extracellular vesicles and explores their therapeutic roles in intervertebral disc degeneration treatment through various mechanisms. These mechanisms include mitigating cell loss and senescence, delaying extracellular matrix degeneration, and modulating the inflammatory microenvironment. Additionally, it highlights recent efforts in engineering extracellular vesicles to enhance their targeting and therapeutic efficacy. The integration of extracellular vesicle-based acellular therapy is anticipated to drive significant advancements in disc regenerative medicine.
The translational potential of this article
Existing clinical treatment strategies often fail to effectively address the challenges associated with regenerating degenerated intervertebral discs. As a new regenerative medicine strategy, the extracellular vesicle strategy avoids the risks associated with cell transplantation and shows great promise in treating intervertebral disc degeneration by carrying therapeutic cargo. This review comprehensively examines the latest research, underlying mechanisms, and therapeutic potential of extracellular vesicles, offering a promising new strategy for intervertebral disc degeneration treatment.
{"title":"Innovating intervertebral disc degeneration therapy: Harnessing the power of extracellular vesicles","authors":"Shanfeng Chen , Yiming Dou , Yiming Zhang , Xun Sun , Xinyu Liu , Qiang Yang","doi":"10.1016/j.jot.2024.09.014","DOIUrl":"10.1016/j.jot.2024.09.014","url":null,"abstract":"<div><div>Intervertebral disc degeneration is the leading cause of low back pain, imposing significant burdens on patients, societies, and economies. Advancements in regenerative medicine have spotlighted extracellular vesicles as promising nanoparticles for intervertebral disc degeneration treatment. Extracellular vesicles retain the potential of cell therapy and serve as carriers to deliver their cargo to target cells, thereby regulating cell activity. This review summarizes the biogenesis and molecular composition of extracellular vesicles and explores their therapeutic roles in intervertebral disc degeneration treatment through various mechanisms. These mechanisms include mitigating cell loss and senescence, delaying extracellular matrix degeneration, and modulating the inflammatory microenvironment. Additionally, it highlights recent efforts in engineering extracellular vesicles to enhance their targeting and therapeutic efficacy. The integration of extracellular vesicle-based acellular therapy is anticipated to drive significant advancements in disc regenerative medicine.</div></div><div><h3>The translational potential of this article</h3><div>Existing clinical treatment strategies often fail to effectively address the challenges associated with regenerating degenerated intervertebral discs. As a new regenerative medicine strategy, the extracellular vesicle strategy avoids the risks associated with cell transplantation and shows great promise in treating intervertebral disc degeneration by carrying therapeutic cargo. This review comprehensively examines the latest research, underlying mechanisms, and therapeutic potential of extracellular vesicles, offering a promising new strategy for intervertebral disc degeneration treatment.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"50 ","pages":"Pages 44-55"},"PeriodicalIF":5.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11761297/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047032","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 : 2025-01-01DOI: 10.1016/j.jot.2024.10.003
Xiaofeng Liu , Yongqiang Zheng , Hao Li , Yiyang Ma , Ruomu Cao , Zhikai Zheng , Yuchen Tian , Lin Du , Jinshan Zhang , Changqing Zhang , Junjie Gao
Osteoarthritis (OA) is a progressive degenerative disease affected by many factors, and there is currently no effective treatment. In recent years, the latest progress in metabolomics in OA research has revealed several metabolic pathways and new specific metabolites involved in OA. Metabolites play significant roles in the identification and management of OA. This review looks back on the development history of metabolomics and the progress of this technology in OA as well as its potential clinical applications. It summarizes the applications of metabolites in the field of OA and future research directions. This understanding will advance the identification of metabolic treatment goals for OA.
The translational potential of this article
The development of metabolomics offers possibilities for the treatment of OA. This article reviews the relationship between metabolites associated with chondrocytes and OA. Selectively altering these three metabolic pathways and their associated metabolites may hold great potential as new focal points for OA treatment.
{"title":"The role of metabolites in the progression of osteoarthritis: Mechanisms and advances in therapy","authors":"Xiaofeng Liu , Yongqiang Zheng , Hao Li , Yiyang Ma , Ruomu Cao , Zhikai Zheng , Yuchen Tian , Lin Du , Jinshan Zhang , Changqing Zhang , Junjie Gao","doi":"10.1016/j.jot.2024.10.003","DOIUrl":"10.1016/j.jot.2024.10.003","url":null,"abstract":"<div><div>Osteoarthritis (OA) is a progressive degenerative disease affected by many factors, and there is currently no effective treatment. In recent years, the latest progress in metabolomics in OA research has revealed several metabolic pathways and new specific metabolites involved in OA. Metabolites play significant roles in the identification and management of OA. This review looks back on the development history of metabolomics and the progress of this technology in OA as well as its potential clinical applications. It summarizes the applications of metabolites in the field of OA and future research directions. This understanding will advance the identification of metabolic treatment goals for OA.</div></div><div><h3>The translational potential of this article</h3><div>The development of metabolomics offers possibilities for the treatment of OA. This article reviews the relationship between metabolites associated with chondrocytes and OA. Selectively altering these three metabolic pathways and their associated metabolites may hold great potential as new focal points for OA treatment.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"50 ","pages":"Pages 56-70"},"PeriodicalIF":5.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047037","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 : 2025-01-01DOI: 10.1016/j.jot.2024.10.006
Xiankun Cao , Kewei Rong , Yinghua Li , Pu Zhang , Kexin Liu , Lei Cui , Shaotian Fu , Qi Hua , Xiao Yang , Hang Zhang , Xiaofei Cheng , Peixiang Ma , Jie Zhao , An Qin
Background
RANKL and SCLEROSTIN antibodies have provided a strong effective choice for treating osteoporosis in the past years, which suggested novel molecular target identification and therapeutic strategies development are important for the treatment of osteoporosis. The therapeutic effect of verapamil, a drug previously used for cardiovascular diseases, on diabetes was due to the inhibition of TXNIP expression, which has also been reported as a target in mice osteoporosis. Whether verapamil-inhibited TXNIP expression is related to osteoporosis and how it works on the molecular level is worthy to be explored.
Methods
The polymorphism genotyping analysis was performed on patients with different degrees of osteoporosis. The responsiveness of bone marrow-derived macrophage cells (bone marrow-derived mesenchymal stem cells) to verapamil was evaluated by CCK-8, TRAP staining assay (ALP and AR staining assay), Bone Resorption Assay, and RNA-Sequencing. The expression and cytoplasmic efflux of ChREBP were determined by western blotting and immunofluorescence. Bilateral ovariectomy models were created, rescued by verapamil injection and the effectiveness was evaluated by Micro-CT and Histological analysis.
Results
Here we discovered that rs7211 single nucleotide polymorphism (SNP) of TXNIP is closely associated with increased femur neck bone mineral density (BMD) and decreased osteoporosis rate, suggesting the importance of TXNIP in the development of osteoporosis. Verapamil suppresses Txnip expression, reduces bone turnover rate and thus rescues ovariectomy-induced mice bone loss. Mechanistically, verapamil promoted ChREBP cytoplasmic efflux, regulated Pparγ expression both mediating Txnip-MAPK, NF- B axis in osteoclasts, and suppressed the ChREBP-Txnip-Bmp2 axis in osteoblasts.
Conclusions
The results of our study show the correlation of rs7211 TXNIP-T allele with Chinese increased femur neck BMD and decreased osteoporosis rate. In addition, verapamil can rescue mice from osteoporosis by regulateing ChREBP, Pparγ-Txnip-MAPK, NF- B axis in osteoclasts and ChREBP-Txnip-Bmp2 axis in osteoblasts.
The translational potential of this article
The inhibition of Txnip by verapamil in osteoclasts and osteoblasts leads to low bone turnover and reduced bilateral ovariectomy-induced mice bone loss, which points out its great clinical translation potential on postmenopausal osteoporosis treatment.
{"title":"A novel application perspective of the clinical-used drug verapamil on osteoporosis via targeting Txnip","authors":"Xiankun Cao , Kewei Rong , Yinghua Li , Pu Zhang , Kexin Liu , Lei Cui , Shaotian Fu , Qi Hua , Xiao Yang , Hang Zhang , Xiaofei Cheng , Peixiang Ma , Jie Zhao , An Qin","doi":"10.1016/j.jot.2024.10.006","DOIUrl":"10.1016/j.jot.2024.10.006","url":null,"abstract":"<div><h3>Background</h3><div>RANKL and SCLEROSTIN antibodies have provided a strong effective choice for treating osteoporosis in the past years, which suggested novel molecular target identification and therapeutic strategies development are important for the treatment of osteoporosis. The therapeutic effect of verapamil, a drug previously used for cardiovascular diseases, on diabetes was due to the inhibition of TXNIP expression, which has also been reported as a target in mice osteoporosis. Whether verapamil-inhibited TXNIP expression is related to osteoporosis and how it works on the molecular level is worthy to be explored.</div></div><div><h3>Methods</h3><div>The polymorphism genotyping analysis was performed on patients with different degrees of osteoporosis. The responsiveness of bone marrow-derived macrophage cells (bone marrow-derived mesenchymal stem cells) to verapamil was evaluated by CCK-8, TRAP staining assay (ALP and AR staining assay), Bone Resorption Assay, and RNA-Sequencing. The expression and cytoplasmic efflux of ChREBP were determined by western blotting and immunofluorescence. Bilateral ovariectomy models were created, rescued by verapamil injection and the effectiveness was evaluated by Micro-CT and Histological analysis.</div></div><div><h3>Results</h3><div>Here we discovered that rs7211 single nucleotide polymorphism (SNP) of <em>TXNIP</em> is closely associated with increased femur neck bone mineral density (BMD) and decreased osteoporosis rate, suggesting the importance of TXNIP in the development of osteoporosis. Verapamil suppresses <em>Txnip</em> expression, reduces bone turnover rate and thus rescues ovariectomy-induced mice bone loss. Mechanistically, verapamil promoted ChREBP cytoplasmic efflux, regulated Pparγ expression both mediating Txnip-MAPK, NF-<span><math><mrow><mi>κ</mi></mrow></math></span> B axis in osteoclasts, and suppressed the ChREBP-Txnip-Bmp2 axis in osteoblasts.</div></div><div><h3>Conclusions</h3><div>The results of our study show the correlation of rs7211 <em>TXNIP-T</em> allele with Chinese increased femur neck BMD and decreased osteoporosis rate. In addition, verapamil can rescue mice from osteoporosis by regulateing ChREBP, Pparγ-Txnip-MAPK, NF-<span><math><mrow><mi>κ</mi></mrow></math></span> B axis in osteoclasts and ChREBP-Txnip-Bmp2 axis in osteoblasts.</div></div><div><h3>The translational potential of this article</h3><div>The inhibition of Txnip by verapamil in osteoclasts and osteoblasts leads to low bone turnover and reduced bilateral ovariectomy-induced mice bone loss, which points out its great clinical translation potential on postmenopausal osteoporosis treatment.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"50 ","pages":"Pages 158-173"},"PeriodicalIF":5.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773151/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059330","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 : 2025-01-01DOI: 10.1016/j.jot.2024.11.009
Ziyang Liu , Chuang Liu , Huan Zhou , Chunyong Liang , Wei Chen , Yanjie Bai , Xinlong Ma , Yingze Zhang , Lei Yang
Objective
Bone injury complicated with bleeding and irregular shaped defect are challenging in orthopedic surgery and practices due to the lack of reliable hemostasis and simultaneous defect repair strategy. Bone wax is a century-old biomaterial for bleeding management in orthopedic surgery, characterized with ready-to-use advantage but the risk of failed bone reunion due to the biological inertness and non-degradability. In current work, integration of bioceramic cement and premixed concept was motivated to prepare a in situ self-setting bioactive calcium phosphate based bone wax (CaPBW) for bone hemostasis and defect repair.
Methods
A moldable, in situ self-setting bioactive CaPBW with a novel formulation of calcium phosphate cement (CPC), monetite (DPCA) granules, modified starch and polyethylene glycol (PEG) was developed for bone hemostasis and defect repair. The CaPBW material was evaluated by characterization, physical and chemical properties, biocompatibility, osteogenic ability and hemostatic ability.
Results
CaPBW adopted the ready-to-use feature of traditional bone wax, showing feasibility in shape molding and defect sealing. When interacted with physiological fluid like blood, CaPBW could transformed from putty to solid state within tens of minutes due to the gradual PEG-water exchange and CPC hydration, providing mechanical stability for bleeding clotting and bone defect filling. In vitro studies revealed the superiority of CaPBW over bone wax in blood coagulation and osteoblast differentiation, along with hemocompatibility and osteogenesis confirmation. In vivo studies demonstrated the reliability of CaPBW in hemostasis and bone regeneration compared to traditional bone wax, promoting the efficacy of bone bleeding and new bone formation.
Conclusion
As compared to traditional bone hemostatic agent bone wax, CaPBW not only preserved its advantages in handling and defect sealing, but also provided platform for temporary physical support and bone regeneration acceleration.
The translational potential of this article
The integrated design of osteogenesis and hemostasis makes CaPBW have the dual functions as bone hemostasis material and artificial bone substitute. CaPBW therefore demonstrates a strategy of next-generation bone wax with high translational potential for orthopedic surgery.
{"title":"Moldable self-setting and bioactive bone wax for bone hemostasis and defect repair","authors":"Ziyang Liu , Chuang Liu , Huan Zhou , Chunyong Liang , Wei Chen , Yanjie Bai , Xinlong Ma , Yingze Zhang , Lei Yang","doi":"10.1016/j.jot.2024.11.009","DOIUrl":"10.1016/j.jot.2024.11.009","url":null,"abstract":"<div><h3>Objective</h3><div>Bone injury complicated with bleeding and irregular shaped defect are challenging in orthopedic surgery and practices due to the lack of reliable hemostasis and simultaneous defect repair strategy. Bone wax is a century-old biomaterial for bleeding management in orthopedic surgery, characterized with ready-to-use advantage but the risk of failed bone reunion due to the biological inertness and non-degradability. In current work, integration of bioceramic cement and premixed concept was motivated to prepare a in situ self-setting bioactive calcium phosphate based bone wax (CaPBW) for bone hemostasis and defect repair.</div></div><div><h3>Methods</h3><div>A moldable, in situ self-setting bioactive CaPBW with a novel formulation of calcium phosphate cement (CPC), monetite (DPCA) granules, modified starch and polyethylene glycol (PEG) was developed for bone hemostasis and defect repair. The CaPBW material was evaluated by characterization, physical and chemical properties, biocompatibility, osteogenic ability and hemostatic ability.</div></div><div><h3>Results</h3><div>CaPBW adopted the ready-to-use feature of traditional bone wax, showing feasibility in shape molding and defect sealing. When interacted with physiological fluid like blood, CaPBW could transformed from putty to solid state within tens of minutes due to the gradual PEG-water exchange and CPC hydration, providing mechanical stability for bleeding clotting and bone defect filling. <em>In vitro</em> studies revealed the superiority of CaPBW over bone wax in blood coagulation and osteoblast differentiation, along with hemocompatibility and osteogenesis confirmation. <em>In vivo</em> studies demonstrated the reliability of CaPBW in hemostasis and bone regeneration compared to traditional bone wax, promoting the efficacy of bone bleeding and new bone formation.</div></div><div><h3>Conclusion</h3><div>As compared to traditional bone hemostatic agent bone wax, CaPBW not only preserved its advantages in handling and defect sealing, but also provided platform for temporary physical support and bone regeneration acceleration.</div></div><div><h3>The translational potential of this article</h3><div>The integrated design of osteogenesis and hemostasis makes CaPBW have the dual functions as bone hemostasis material and artificial bone substitute. CaPBW therefore demonstrates a strategy of next-generation bone wax with high translational potential for orthopedic surgery.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"50 ","pages":"Pages 223-234"},"PeriodicalIF":5.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080384","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 : 2025-01-01DOI: 10.1016/j.jot.2024.10.009
Xinyi Liu , Xiaolei Guo , Yixuan Amy Pei , Ming Pei , Zigang Ge
Functional cartilage regeneration remains difficult to achieve despite decades of research. Dozens of commercial products have been proposed, with each targeting different facets of successful cartilage engineering, including mechanical properties, integration, lubrication and inflammation; however, there remains a lack of breakthroughs in meaningful clinical outcomes. Prior research categorized commercial products based on their components and elucidated challenges faced during the market approval process. This paper, for the first time, comprehensively reviews the properties of commercial products covering the last 25 years, including design trends in components, compatibility with minimally invasive surgery, indications for cartilage defects, long-term follow-up, as well as active sponsorship support of the International Cartilage Regeneration and Joint Preservation Society (ICRS). We aim to summarize the key factors for potentially successful commercial products and elucidate overarching trends in technology development in this field. Given that no revolutionary products have yielded significantly improved clinical results, emerging products compete with one another on user-friendliness and cost-efficiency. Other relevant characteristics include compatibility with minimally invasive surgery, extensiveness of required surgery (one-stage vs. two-stage), use of versatile artificial polymers and application of cells and biomaterials. Specific products continue to lead the market due to their cost-efficiency or indications for larger cartilage defects. However, they have been shown to result in no significant improvement upon clinical follow-up. Thus, there is a need for products that surpass current commercial products and show clinical effectiveness.
Translation potential of this article: This review analyzes product components, compatibility with minimally invasive surgery, indication for cartilage defect areas, clinical performance as well as sponsorship for the World Conference of International Cartilage Regeneration & Joint Preservation Society, based on information about cartilage regeneration products from 1997 to 2023. It shines a light on future development of design and commercialization of cartilage products.
{"title":"Charting a quarter-century of commercial cartilage regeneration products","authors":"Xinyi Liu , Xiaolei Guo , Yixuan Amy Pei , Ming Pei , Zigang Ge","doi":"10.1016/j.jot.2024.10.009","DOIUrl":"10.1016/j.jot.2024.10.009","url":null,"abstract":"<div><div>Functional cartilage regeneration remains difficult to achieve despite decades of research. Dozens of commercial products have been proposed, with each targeting different facets of successful cartilage engineering, including mechanical properties, integration, lubrication and inflammation; however, there remains a lack of breakthroughs in meaningful clinical outcomes. Prior research categorized commercial products based on their components and elucidated challenges faced during the market approval process. This paper, for the first time, comprehensively reviews the properties of commercial products covering the last 25 years, including design trends in components, compatibility with minimally invasive surgery, indications for cartilage defects, long-term follow-up, as well as active sponsorship support of the International Cartilage Regeneration and Joint Preservation Society (ICRS). We aim to summarize the key factors for potentially successful commercial products and elucidate overarching trends in technology development in this field. Given that no revolutionary products have yielded significantly improved clinical results, emerging products compete with one another on user-friendliness and cost-efficiency. Other relevant characteristics include compatibility with minimally invasive surgery, extensiveness of required surgery (one-stage vs. two-stage), use of versatile artificial polymers and application of cells and biomaterials. Specific products continue to lead the market due to their cost-efficiency or indications for larger cartilage defects. However, they have been shown to result in no significant improvement upon clinical follow-up. Thus, there is a need for products that surpass current commercial products and show clinical effectiveness.</div><div><strong>Translation potential of this article</strong>: This review analyzes product components, compatibility with minimally invasive surgery, indication for cartilage defect areas, clinical performance as well as sponsorship for the World Conference of International Cartilage Regeneration & Joint Preservation Society, based on information about cartilage regeneration products from 1997 to 2023. It shines a light on future development of design and commercialization of cartilage products.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"50 ","pages":"Pages 354-363"},"PeriodicalIF":5.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143177861","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 : 2025-01-01DOI: 10.1016/j.jot.2025.01.015
Sebastian Simon , Luca Martalanz , Bernhard J.H. Frank , Susana Gardete Hartmann , Jennyfer A. Mitterer , Sujeesh Sebastian , Stephanie Huber , Jochen G. Hofstaetter
{"title":"Corrigendum to ‘Prevalence, risk factors, microbiological results and clinical outcome in unexpected positive intraoperative cultures in unclear and presumed aseptic hip and knee revision arthroplasties - A ten-year retrospective analysis with a minimum follow up of 2 years’ [J Orthop Transl 48 (2024) 156–162]","authors":"Sebastian Simon , Luca Martalanz , Bernhard J.H. Frank , Susana Gardete Hartmann , Jennyfer A. Mitterer , Sujeesh Sebastian , Stephanie Huber , Jochen G. Hofstaetter","doi":"10.1016/j.jot.2025.01.015","DOIUrl":"10.1016/j.jot.2025.01.015","url":null,"abstract":"","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"50 ","pages":"Page 423"},"PeriodicalIF":5.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143600498","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 : 2025-01-01DOI: 10.1016/j.jot.2024.10.010
Yiming Zhang , Jingzhou Yang , Wentao Wan , Qingqian Zhao , Mingyuan Di , Dachen Zhang , Gang Liu , Chao Chen , Xun Sun , Wei Zhang , Hanming Bian , Yang Liu , Ye Tian , Lu Xue , Yiming Dou , Zheng Wang , Qiulin Li , Qiang Yang
<div><h3>Background</h3><div>The materials for artificial bone scaffolds have long been a focal point in biomaterials research. Tantalum, with its excellent bioactivity and tissue compatibility, has gradually become a promising alternative material. 3D printing technology shows unique advantages in designing complex structures, reducing costs, and providing personalized customization in the manufacture of porous tantalum fusion cages. Here we report the pre-clinical large animal (sheep) study on the newly developed 3D printed biomimetic trabecular porous tantalum fusion cage for assessing the long-term intervertebral fusion efficacy and safety.</div></div><div><h3>Methods</h3><div>Porous tantalum fusion cages were fabricated using laser powder bed fusion (LPBF) and chemical vapor deposition (CVD) methods. The fusion cages were characterized using scanning electron microscopy (SEM) and mechanical compression tests. Small-Tailed Han sheep served as the animal model, and the two types of fusion cages were implanted in the C3/4 cervical segments and followed for up to 12 months. Imaging techniques, including X-ray, CT scans, and Micro CT, were used to observe the bone integration of the fusion cages. Hard tissue sections were used to assess osteogenic effects and bone integration. The range of motion (ROM) of the motion segments was evaluated using a biomechanical testing machine. Serum biochemical indicators and pathological analysis of major organs were conducted to assess biocompatibility.</div></div><div><h3>Results</h3><div>X-ray imaging showed that both the 3D-printed and chemical vapor deposition porous tantalum fusion cages maintained comparable average intervertebral disc heights. Due to the presence of metal artifacts, CT and Micro CT imaging could not effectively analyze bone integration. Histomorphology data indicated that both the 3D-printed and chemical vapor deposition porous tantalum fusion cages exhibited similar levels of bone contact and integration at 3, 6, and 12 months, with bone bridging observed at 12 months. Both groups of fusion cages demonstrated consistent mechanical stability across all time points. Serum biochemistry showed no abnormalities, and no significant pathological changes were observed in the heart, liver, spleen, lungs, and kidneys.</div></div><div><h3>Conclusion</h3><div>This study confirms that 3D-printed and chemical vapor deposition porous tantalum fusion cages exhibit comparable, excellent osteogenic effects and long-term biocompatibility. Additionally, 3D-printed porous tantalum fusion cages offer unique advantages in achieving complex structural designs, low-cost manufacturing, and personalized customization, providing robust scientific support for future clinical applications.</div></div><div><h3>The translational potential of this article</h3><div>The translational potential of this paper is to use 3D printed biomimetic trabecular porous tantalum spine fusion cage with bone trabecular structure and val
{"title":"Evaluation of biological performance of 3D printed trabecular porous tantalum spine fusion cage in large animal models","authors":"Yiming Zhang , Jingzhou Yang , Wentao Wan , Qingqian Zhao , Mingyuan Di , Dachen Zhang , Gang Liu , Chao Chen , Xun Sun , Wei Zhang , Hanming Bian , Yang Liu , Ye Tian , Lu Xue , Yiming Dou , Zheng Wang , Qiulin Li , Qiang Yang","doi":"10.1016/j.jot.2024.10.010","DOIUrl":"10.1016/j.jot.2024.10.010","url":null,"abstract":"<div><h3>Background</h3><div>The materials for artificial bone scaffolds have long been a focal point in biomaterials research. Tantalum, with its excellent bioactivity and tissue compatibility, has gradually become a promising alternative material. 3D printing technology shows unique advantages in designing complex structures, reducing costs, and providing personalized customization in the manufacture of porous tantalum fusion cages. Here we report the pre-clinical large animal (sheep) study on the newly developed 3D printed biomimetic trabecular porous tantalum fusion cage for assessing the long-term intervertebral fusion efficacy and safety.</div></div><div><h3>Methods</h3><div>Porous tantalum fusion cages were fabricated using laser powder bed fusion (LPBF) and chemical vapor deposition (CVD) methods. The fusion cages were characterized using scanning electron microscopy (SEM) and mechanical compression tests. Small-Tailed Han sheep served as the animal model, and the two types of fusion cages were implanted in the C3/4 cervical segments and followed for up to 12 months. Imaging techniques, including X-ray, CT scans, and Micro CT, were used to observe the bone integration of the fusion cages. Hard tissue sections were used to assess osteogenic effects and bone integration. The range of motion (ROM) of the motion segments was evaluated using a biomechanical testing machine. Serum biochemical indicators and pathological analysis of major organs were conducted to assess biocompatibility.</div></div><div><h3>Results</h3><div>X-ray imaging showed that both the 3D-printed and chemical vapor deposition porous tantalum fusion cages maintained comparable average intervertebral disc heights. Due to the presence of metal artifacts, CT and Micro CT imaging could not effectively analyze bone integration. Histomorphology data indicated that both the 3D-printed and chemical vapor deposition porous tantalum fusion cages exhibited similar levels of bone contact and integration at 3, 6, and 12 months, with bone bridging observed at 12 months. Both groups of fusion cages demonstrated consistent mechanical stability across all time points. Serum biochemistry showed no abnormalities, and no significant pathological changes were observed in the heart, liver, spleen, lungs, and kidneys.</div></div><div><h3>Conclusion</h3><div>This study confirms that 3D-printed and chemical vapor deposition porous tantalum fusion cages exhibit comparable, excellent osteogenic effects and long-term biocompatibility. Additionally, 3D-printed porous tantalum fusion cages offer unique advantages in achieving complex structural designs, low-cost manufacturing, and personalized customization, providing robust scientific support for future clinical applications.</div></div><div><h3>The translational potential of this article</h3><div>The translational potential of this paper is to use 3D printed biomimetic trabecular porous tantalum spine fusion cage with bone trabecular structure and val","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"50 ","pages":"Pages 185-195"},"PeriodicalIF":5.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786794/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080341","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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