Journal of Orthopaedic Translation最新文献

{"title":"Osteoclast-derived apoptotic bodies accelerate the pathological progression of osteoarthritis via disturbing subchondral bone remodeling","authors":"Hongbo Ai ,&nbsp;Ce Dou ,&nbsp;Yutong Wu ,&nbsp;Dongyang Zhang ,&nbsp;Ziyang Zhang ,&nbsp;Chao Zhang ,&nbsp;Yuhang Xi ,&nbsp;Ying Qu ,&nbsp;Jiulin Tan ,&nbsp;Pengbin Yin ,&nbsp;Jianzhong Xu ,&nbsp;Shuquan Guo ,&nbsp;Fei Luo","doi":"10.1016/j.jot.2025.01.004","DOIUrl":"10.1016/j.jot.2025.01.004","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the role of osteoclast-derived apoptotic bodies (OC-ABs) in osteoarthritis (OA), specifically their impact on subchondral bone remodeling and disease progression, and to explore potential therapeutic strategies targeting OC-AB-induced pathways.</div></div><div><h3>Methods</h3><div>We utilized a mouse model of anterior cruciate ligament transection (ACLT) to simulate post-traumatic osteoarthritis (PTOA). Levels of OC-ABs were assessed in subchondral bone and correlated with OA severity. Additionally, apoptotic body-deficient MRL/lpr mice were analyzed to evaluate the direct contribution of OC-ABs to OA progression and subchondral bone remodeling. The involvement of OC-ABs in osteogenesis was further examined using mesenchymal stem cells (MSCs), with a focus on the RANKL reverse signaling pathway. The therapeutic potential of rapamycin to counteract OC-AB effects was tested.</div></div><div><h3>Results</h3><div>Increased OC-AB accumulation in subchondral bone was positively correlated with OA severity in ACLT-induced mice. Apoptotic body-deficient MRL/lpr mice demonstrated slower OA progression and maintained more stable subchondral bone architecture, indicating a pathogenic role of OC-ABs in OA. OC-ABs significantly stimulated osteogenesis in MSCs via the RANKL reverse signaling pathway. Treatment with rapamycin effectively reversed OC-AB-induced subchondral bone formation, mitigated OA progression, and inhibited the RANKL reverse signaling pathway.</div></div><div><h3>Conclusion</h3><div>OC-ABs play a critical role in exacerbating OA by promoting subchondral bone remodeling via the RANKL reverse signaling pathway. Rapamycin presents as a promising therapeutic agent capable of mitigating OC-AB-driven pathology, highlighting new avenues for targeted OA treatment.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"51 ","pages":"Pages 108-118"},"PeriodicalIF":5.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143562611","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}

{"title":"Emerging role of macrophages in neuropathic pain","authors":"Si-Han Tong ,&nbsp;De-Lin Liu ,&nbsp;Peng Liao ,&nbsp;Sen-Yao Zhang ,&nbsp;Jian Zhou ,&nbsp;Yao Zong ,&nbsp;Chang-Qing Zhang ,&nbsp;Yi-Gang Huang ,&nbsp;Jun-Jie Gao","doi":"10.1016/j.jot.2025.01.016","DOIUrl":"10.1016/j.jot.2025.01.016","url":null,"abstract":"<div><div>Neuropathic pain is a complex syndrome caused by injury to the neurons, which causes persistent hypersensitivity and considerable inconvenience to the patient's whole life. Over the past two decades, the interaction between immune cells and neurons has been proven to play a crucial role in the development of neuropathic pain. Increasing studies have indicated the important role of macrophages for neuroinflammation and have shed light on the underlying molecular and cellular mechanisms. In addition, novel therapeutic methods targeting macrophages are springing up, which provide more options in our clinical treatment. Herein, we reviewed the characteristics of peripheral macrophages and their function in neuropathic pain, with the aim of better understanding how these cells contribute to pathological processes and paving the way for therapeutic approaches.</div></div><div><h3>Translational potential statement</h3><div>This review provides a comprehensive overview of the mechanisms underlying the interplay between the macrophages and nervous system during the progression of nerve injury. Additionally, it compiles existing intervention strategies targeting macrophages for the treatment of neuropathic pain. This information offers valuable insights for researchers seeking to address the challenge of this intractable pain.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"51 ","pages":"Pages 227-241"},"PeriodicalIF":5.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143642082","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}

{"title":"Epidemiological trends and characteristics of osteoarthritis in China during 1990–2021","authors":"Sheng Chen ,&nbsp;Mingjue Chen ,&nbsp;Chao Chen ,&nbsp;Chao Xie ,&nbsp;Yihan Yu ,&nbsp;Zengwu Shao ,&nbsp;Guozhi Xiao","doi":"10.1016/j.jot.2025.02.006","DOIUrl":"10.1016/j.jot.2025.02.006","url":null,"abstract":"<div><h3>Background</h3><div>This study aimed to comprehensively analyze the incidence, prevalence, and disability-adjusted life years (DALYs) of osteoarthritis (OA) in China from 1990 to 2021 by age, sex, joint sites, high body mass index (BMI) and sociodemographic index (SDI).</div></div><div><h3>Methods</h3><div>Data and methodologies from the Global Burden of Diseases (GBD) Study 2021 were obtained to evaluate the burden of OA in China. This assessment was conducted by estimating the number of incident cases, prevalent cases, DALYs, and corresponding age-standardized rates (ASRs). The estimated annual percentage change was employed to delineate the trends over time.</div></div><div><h3>Results</h3><div>In China, the number of OA incidence cases, prevalence cases, and DALYs increased to 11.65 million, 152.85 million and 5.33 million in 2021, respectively, exhibiting a consistent upward trend over the years. The ASRs of OA incidence, prevalence, and DALYs rose 13.86 %, 14.34 %, and 16.23 % from 1990 to 2021, respectively, with knee OA most affected. In 2021, OA incidence, prevalence, and DALYs were higher in women than in men, and increased with age for both sexes, peaking at ages 50–54 for incidence and 55–59 for prevalence and DALYs. DALYs of OA attributed to high BMI increased rapidly, and high BMI contributed to 21.64 % of the total age-standardized DALYs rate of OA in China. Positive correlations were observed between ASRs and China's SDI from 1990 to 2021.</div></div><div><h3>Conclusion</h3><div>OA constitutes a significant public health challenge in China, with a persistently high disease burden. There is a pressing need to enhance public understanding of the risk factors associated with OA and to promote preventive strategies to mitigate the future burden of this disorder.</div><div>The translational potential of this article China has the largest elderly population and the highest prevalence of OA globally. Updating and analyzing epidemiological data of OA in China will offer the public, healthcare professionals, and policymakers the most current, comprehensive, and comparable information, which holds significant translational potential.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"51 ","pages":"Pages 218-226"},"PeriodicalIF":5.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143642085","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}

{"title":"The role of Piezo1 in bone marrow stem cells in response to elevated intraosseous pressure on regulating osteogenesis and angiogenesis of steroid-induced osteonecrosis of the femoral head","authors":"Zilin Li ,&nbsp;Lizhi Han ,&nbsp;Bo Wang ,&nbsp;Ping Wang ,&nbsp;Yuxi Wang ,&nbsp;Ruoyu Wang ,&nbsp;Xiao Lv ,&nbsp;Yong Feng","doi":"10.1016/j.jot.2025.01.008","DOIUrl":"10.1016/j.jot.2025.01.008","url":null,"abstract":"<div><h3>Objectives</h3><div>Steroid-induced osteonecrosis of the femoral head (SONFH) remains a significant global health issue, with an unclear pathogenesis. Elevated intraosseous pressure is considered a key initiating factor in SONFH development. Impaired osteogenesis and angiogenesis are believed to be critical in SONFH progression. Piezo1, a mechanosensitive cation channel, may sense changes in intraosseous pressure. In this study, we set out to explore the role of Piezo1 in SONFH and how to target Piezo1 to treat SONFH.</div></div><div><h3>Methods</h3><div>Femoral head tissue specimens were collected from patients with ONFH and femoral neck fracture. Histological staining, Western blotting, and RT-PCR analysis were conducted to investigate the relationship between elevated intraosseous pressure and SONFH in rat models. Immunofluorescence staining of femoral head tissues was performed to study the spatiotemporal relationship between elevated intraosseous pressure and angiogenesis, osteogenesis, and development of SONFH.</div></div><div><h3>Results</h3><div>In the early stages of SONFH, elevated intraosseous pressure increased angiogenesis and osteogenesis. However, as the pressure continued to rise, both processes were inhibited. Furthermore, Elevated intraosseous pressure activated the Piezo1 signaling pathway in bone marrow stem cells. Piezo1 activation led to increased intracellular calcium influx, thus enhancing osteogenesis and angiogenesis through CAM-NFAT1 signaling pathway.</div></div><div><h3>Conclusion</h3><div>In the early stages of SONFH, Piezo1 in BMSCs senses increased intraosseous pressure, promoting angiogenesis and osteogenesis. Targeting Piezo1 to promote the osteogenic and angiogenic potential of stem cells, which could curb further increases in pressure, contribute to early treatment of SONFH.</div></div><div><h3>The translational potential of this article</h3><div>Currently, many mechanisms of the impact of elevated intraosseous pressure on osteonecrosis of the femoral head are still in the basic theoretical research stage, and we hope to translate them into clinical applications as soon as possible. We discovered that targeting Piezo1 curb further increases in intraosseous pressure, alleviating the damaging effects of glucocorticoids on stem cells and blood vessels, which exerting great significance in treatment of early stage SONFH.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"51 ","pages":"Pages 278-289"},"PeriodicalIF":5.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143645022","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}

{"title":"Associations of metabolic status with all-cause mortality among individuals with osteoarthritis: A prospective cohort study","authors":"Hao Yang ,&nbsp;Muhui Zeng ,&nbsp;Tianxiang Fan ,&nbsp;Haowei Chen ,&nbsp;Xiaofeng Fang ,&nbsp;Zhong Alan Li ,&nbsp;Xiaoshuai Wang ,&nbsp;David J. Hunter ,&nbsp;Changhai Ding ,&nbsp;Zhaohua Zhu","doi":"10.1016/j.jot.2025.02.004","DOIUrl":"10.1016/j.jot.2025.02.004","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Individuals with osteoarthritis (OA) often experience significant changes in their metabolic status and have a higher risk of mortality compared to the general population. However, no study has quantified the metabolic status of OA patients. Moreover, the association between metabolic status and risk of mortality among OA patients remains unclear.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;The analysis included baseline populations with OA from the UK Biobank (UKBB) study and the National Health and Nutrition Examination Survey (NHANES) 1999–2018. Metabolic status was assessed using composite scores based on body mass index, waist-hip ratio, blood pressure, fasting plasma glucose, hemoglobin A1c, C-reactive protein, triacylglycerols, and lipoproteins. Restricted cubic splines were used to define healthy ranges for each indicator regarding mortality risk. Factors received 1 if within a healthy range, else 0. Total scores ranged from 0 to 7, with 3+ indicating good metabolic health. The traditional metabolic syndrome criteria (ATP III) and the Strict definition were used for comparison. Associations between metabolic unhealth and mortality were examined using Cox proportional hazards models. Integrated Discrimination Improvement (IDI) evaluated discriminatory capacity, and Net Reclassification Improvement (NRI) assessed reclassification performance in predicting ten-year mortality.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Among 44,302 UKBB OA participants, 36.0 % were metabolically unhealthy (scores: 0–2), while in 5233 NHANES OA participants, 39.1 % were metabolically unhealthy based on our newly-established definition. After adjustment for covariates, metabolically unhealthy individuals had significantly higher all-cause mortality risk (HR: 1.36; 95 % CI: 1.26–1.47 in UKBB; HR: 1.16; 95 % CI: 1.03–1.30 in NHANES) compared to metabolically healthy individuals. In UKBB, compared to ATP III definition, the changes in IDI and NRI for our newly-established definition were 0.10 % (0.01 %, 0.20 %) and 10.60 % (1.8 %, 13.60 %), respectively. When the comparison was made with the Strict definition, the newly-established definition showed changes in IDI and NRI of 0.18 % (0.10 %, 0.20 %) and 12.10 % (10.30 %, 13.80 %), respectively. results.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;A new definition for quantifying metabolic unhealth in OA was proposed. It identified a significant mortality risk with poorer metabolic status and outperformed general definitions in predictive accuracy. conclusion.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;The translational potential of this article&lt;/h3&gt;&lt;div&gt;OA is the leading joint disease worldwide, carrying a heavy health burden. Our newly established definition, evaluating metabolic health through waist-to-hip ratio, BMI, blood pressure, glucose, lipids, and C-reactive protein, identified 36.0 % OA patients in UK Biobank and 39.1 % OA patients in NHANES as having poor metabolic status, which is applicable in clinical and resea","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"51 ","pages":"Pages 207-217"},"PeriodicalIF":5.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143631878","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}

{"title":"Inhibition of ERK1/2 mediated activation of Drp1 alleviates intervertebral disc degeneration via suppressing pyroptosis and apoptosis in nucleus pulposus cells","authors":"Shenkai Su ,&nbsp;Xuanzhang Wu ,&nbsp;Bin Li ,&nbsp;Fengyu Zhang ,&nbsp;Kaiying Zhang ,&nbsp;Hui Wang ,&nbsp;Yan Lin ,&nbsp;Jiaoxiang Chen","doi":"10.1016/j.jot.2025.01.013","DOIUrl":"10.1016/j.jot.2025.01.013","url":null,"abstract":"<div><h3>Objective</h3><div>Dynamin-related protein 1 (Drp1) plays a crucial role in various inflammatory and degenerative diseases, yet its involvement in intervertebral disc degeneration (IVDD) remains poorly understood. This study aims to elucidate the mechanism by which Drp1 contributes to IVDD and to identify the efficacy of the Drp1 inhibitor Mdivi-1 on IVDD.</div></div><div><h3>Methods</h3><div>Tert-butyl hydroperoxide (TBHP) is utilized to induce an oxidative stress microenvironment <em>in vitro</em>. <em>In vivo</em>, IVDD model is constructed in 8-week old rats through puncture operation. The therapeutic effect of Mdivi-1 is evaluated through X-ray, MRI and histological analysis. A comprehensive set of experiments, including single-cell sequencing analysis, western blot, flow cytometry and immunofluorescence staining, are conducted to investigate the role and underlying mechanisms of Drp1 <em>in vitro</em>.</div></div><div><h3>Results</h3><div>Our study demonstrates that the expression of Drp1 and phosphorylated Drp1 (p-Drp1) are up-regulated in degenerative nucleus pulposus cells (NPCs), which are accompanied with increased pyroptosis and apoptosis. <em>In vivo</em>, both si-Drp1-mediated Drp1 knockdown and the pharmacological inhibitor Mdivi-1 alleviate puncture-induced IVDD in rats. <em>In vitro</em>, si-Drp1 or Mdivi-1 inhibits mitochondria-dependent apoptosis and pyroptosis triggered by TBHP. Mechanistically, Mdivi-1 reduces p-Drp1 levels, inhibits excessive mitochondrial fission, and mitigates mitochondrial dysfunction. Drp1 phosphorylation-based Drp1 mitochondrial translocation and subsequent apoptosis and pyroptosis are regulated by ERK1/2 phosphorylation in NPCs under oxidative stress condition.</div></div><div><h3>Conclusion</h3><div>This study highlights the involvement of Drp1 in the pathological progression of degenerative NPCs in IVDD, which is regulated by ERK1/2. Pharmacological inhibition of Drp1 with Mdivi-1 protects NPCs by promoting mitochondrial function and attenuating apoptosis and pyroptosis. These findings suggest that Mdivi-1 is a promising therapeutic candidate for IVDD treatment.</div></div><div><h3>Translational Potential</h3><div>By offering experimental evidence on the role and mechanism of Drp1 in IVDD, this study underscores the potential of Mdivi-1 as a therapeutic strategy for IVDD.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"51 ","pages":"Pages 163-175"},"PeriodicalIF":5.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143610179","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}

{"title":"Hip joint-preserving strategies for treating osteonecrosis of the femoral head: From nonoperative to operative procedures","authors":"Tanqiu Qi ,&nbsp;Yan Yan ,&nbsp;William Qi ,&nbsp;Weiheng Chen ,&nbsp;Haisheng Yang","doi":"10.1016/j.jot.2025.02.001","DOIUrl":"10.1016/j.jot.2025.02.001","url":null,"abstract":"<div><div>Osteonecrosis of the femoral head (ONFH) has an exceedingly high prevalence and disability rate, causing a tremendous socioeconomic burden. The prevalence of ONFH is increasing, while the population of the patients with ONFH is becoming younger. Once the femoral head collapses, treatment becomes difficult and often requires a hip joint replacement, which is not favorable for young patients. Therefore, hip joint-preserving treatments at an early stage of ONFH are particularly important. This study provides a comprehensive review on hip-preserving strategies for treating ONFH, including nonoperative treatments (e.g., protective weight bearing, hyperbaric oxygen, pulsed electromagnetic, extracorporeal shockwave, bisphosphonate, anticoagulants, hypolipidemics, vasodilators, and traditional Chinese medicine) and operative treatments (e.g., core decompression, osteotomy, bone grafting, mesenchymal stem cell transplantation, tantalum rods, and tissue engineering). Nonoperative treatments aim to slow down the progression of the disease and delay the need for joint replacement; however, they usually cannot effectively prevent the progression of the disease, except in cases of small necrosis areas (&lt;10 %). Additionally, nonoperative treatments have unclear mechanisms that require further investigation. In contrast, operative treatments may stop the negative outcomes of necrosis and therefore appear to be more promising. Currently, an emerging area in operative treatments is regenerative medicine, which could promote the generation of bone tissues and blood vessels and restore hip joint function to pre-necrotic levels as much as possible. This review seeks to not only provide an important reference for clinicians when choosing appropriate strategies for treating ONFH but also offer certain guidance for future basic research in developing ONFH treatments.</div></div><div><h3>The translational potential of this article</h3><div>The incidence of ONFH is increasing, and patients are becoming younger on average. Therefore, the development of hip joint-preserving strategies to treat ONFH at earlier stages is urgently needed, particularly for young patients. However, a comprehensive review is lacking regarding the currently-available hip joint-preserving strategies and their effectiveness. This study is motivated to fill this gap and serve as an important reference for clinicians in choosing appropriate strategies to treat ONFH.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"51 ","pages":"Pages 256-277"},"PeriodicalIF":5.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143644318","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}

{"title":"JP4-039 protects chondrocytes from ferroptosis to attenuate osteoarthritis progression by promoting Pink1/Parkin-dependent mitophagy","authors":"Ya Xie ,&nbsp;Zhongyang Lv ,&nbsp;Weitong Li ,&nbsp;JinTao Lin ,&nbsp;Wei Sun ,&nbsp;Hu Guo ,&nbsp;Xiaoyu Jin ,&nbsp;Yuan Liu ,&nbsp;Ruiyang Jiang ,&nbsp;Yuxiang Fei ,&nbsp;Rui Wu ,&nbsp;Dongquan Shi","doi":"10.1016/j.jot.2025.01.001","DOIUrl":"10.1016/j.jot.2025.01.001","url":null,"abstract":"<div><h3>Background</h3><div>Osteoarthritis (OA) is the most common degenerative joint disease, and its main pathological mechanism is articular cartilage degeneration. The purpose of this study was to investigate the role of mitophagy in the pathogenesis of chondrocyte ferroptosis in OA.</div></div><div><h3>Methods</h3><div>The expressions of ferroptosis related proteins (GPX4, FTH1, COX2) and ubiquitin-dependent mitophagy related proteins (PARKIN, PINK1) in the intact and injured areas of OA cartilage were analyzed. Nitro oxide JP4-039, a mitochondrial targeting antioxidant, has bifunctional role of targeting mitochondria. Then we evaluated the potential protective effect of JP4-039 in OA using the destabilization of medial meniscus (DMM)-induced OA model, as well as tert-butyl hydrogen peroxide (TBHP)-treated primary mouse chondrocytes and human cartilage explants.</div></div><div><h3>Results</h3><div>The concentrations of iron and lipid peroxidation and the expression of ferroptosis drivers in the damaged areas of human OA cartilages were significantly higher than those in the intact cartilage. Pink1/Parkin-dependent mitophagy decreased in the injured area of human OA cartilage and was negatively correlated with ferroptosis. Then, the toxicity and effectiveness of JP4-039 are tested to determine its working concentration. Next, at the molecular biological level, we found that JP4-039 showed the effect of anti-chondrocyte ferroptosis. Moreover, it was verified on DMM-induced OA model mice, that JP4-039 could delay the progression of OA. Finally, JP4-039 was re-verified in vivo and in vitro to inhibit chondrocyte ferroptosis and delay the progression of OA by promoting Pink1/Parkin-dependent mitophagy.</div></div><div><h3>Conclusion</h3><div>JP4-039 inhibits ferroptosis of chondrocytes by promoting Pink1/Parkin-dependent mitophagy and delays OA progression.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"51 ","pages":"Pages 132-144"},"PeriodicalIF":5.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578970","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}

{"title":"Targeted activation on Bnip3 enhances mitophagy to prevent the progression of osteoarthritis","authors":"Yong Gou ,&nbsp;Chenggui Wang ,&nbsp;Kejian Fu ,&nbsp;Shenkai Su ,&nbsp;Hangjin Zhou ,&nbsp;Chunkai Bao ,&nbsp;Hui Nan ,&nbsp;Xiang Zhang ,&nbsp;Yiyuan Xu ,&nbsp;Qi Chen ,&nbsp;Xinchen Gu ,&nbsp;Baiting Chen ,&nbsp;Lin Zheng ,&nbsp;Chenglong Xie ,&nbsp;Man Zhang ,&nbsp;Enxing Xue ,&nbsp;Jiawei Li","doi":"10.1016/j.jot.2025.01.012","DOIUrl":"10.1016/j.jot.2025.01.012","url":null,"abstract":"<div><h3>Background</h3><div>The production of reactive oxygen species (ROS) and mitochondrial dysfunction in chondrocytes are closely related to cartilage degeneration in the procedure of osteoarthritis (OA). Mitophagy is responsible for the scavenging of ROS and dysfunctional mitochondria and is considered a key therapeutic target for the treatment of OA. Tiopronin, a classic thiol antioxidant, has been widely studied for the treatment of various oxidative stress-related diseases.</div></div><div><h3>Methods</h3><div>The expression of mitophagy (PINK1, PARKIN, and TOMM20) in intact and damaged cartilage of OA patients was analyzed by Western blot and histological analysis. RNA sequencing (RNA-seq) analysis was performed to explore the molecular mechanism of tiopronin in regulating mitophagy in chondrocytes, and then to find the specific target of tiopronin. The therapeutic effects of tiopronin were evaluated in the OA model induced by destabilisation of the medial meniscus (DMM), chondrocytes degenerative model with the primary chondrocytes from mouse and human cartilage explants experiment. The downstream molecular mechanisms of tiopronin were further investigated by si-RNA knockdown of mitophagy-related proteins.</div></div><div><h3>Results</h3><div>The level of mitophagy in cartilage was negatively correlated with the severity of OA. We revealed that tiopronin promoted the anabolism of the extracellular matrix (ECM) of hyaline chondrocytes and alleviates ROS <em>in vitro</em> and <em>in vivo</em> by strengthening mitophagy. Moreover, tiopronin strongly activated the expression of Bnip3, a protein anchored in the mitochondrial membrane, and subsequently enhanced the Pink1/Parkin signaling pathway.</div></div><div><h3>Conclusion</h3><div>These findings indicate that the Bnip3-Pink1-Parkin signaling pathway, targeted and activated by tiopronin, plays a key role in inhibiting the progression of OA.</div></div><div><h3>The translational potential of this article</h3><div>As a classical drug in clinic, tiopronin was developed a new therapeutic approach in the treatment in OA via this study. Based the significant and efficient effect of tiopronin in inhibiting the cartilage degermation and delay the progression of OA, it was believed that tiopronin may become an effective therapeutic candidate for OA treatment in clinical settings</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"51 ","pages":"Pages 242-255"},"PeriodicalIF":5.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143644326","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}

{"title":"Internal fixation with biodegradable high purity magnesium screws in the treatment of ankle fracture","authors":"De-Wei Zhao ,&nbsp;Tian-Wei Zhang ,&nbsp;Wei-Dan Wang ,&nbsp;Zi-Ming Wang ,&nbsp;Fu-Yang Wang ,&nbsp;Xing Yang ,&nbsp;Rong-Hua Li ,&nbsp;Liang-Liang Cheng ,&nbsp;Yu Zhang ,&nbsp;Hui-Ya Wang ,&nbsp;Wang-Wei Zhu ,&nbsp;Shi-Bo Huang ,&nbsp;Wei-Rong Li ,&nbsp;Ling Qin","doi":"10.1016/j.jot.2025.01.005","DOIUrl":"10.1016/j.jot.2025.01.005","url":null,"abstract":"<div><h3>Background</h3><div>Metal plates and screws are widely used as internal fixations in the treatment of ankle fracture. However, there are many disadvantages such as \"stress shielding\" effect and the need for secondary surgical removal, which potentially affected the blood supply around the fracture site. In recent years, many studies confirmed that the biodegradable high purity magnesium (Mg) screws exhibited sufficient mechanical strength with adequate degradation rate for effective bone healing, avoiding the need for implant removal operations.</div></div><div><h3>Method</h3><div>We conducted a prospective study on patients with ankle fractures treated at Affiliated Zhongshan Hospital of Dalian University between January 2020 and January 2021. Twenty-four patients (twelve patients for each group) with ankle fractures were treated with high purity Mg screws or conventional titanium alloy plates and screws. Hematological examinations were performed in the early postoperative period, X-ray examinations were performed in the long-term postoperative follow-up. Postoperative complications, including infection, failure of internal fixation and malunion, were recorded during the follow-up. The visual analogue scale (VAS) was used to evaluate postoperative pain perceived by the patients, and the American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot scoring system was used to evaluate their postoperative ankle function.</div></div><div><h3>Results</h3><div>All patients achieved good fracture alignment, and imaging examination showed that the biodegradable high purity Mg screws degraded gradually without breakage or displacement. None of the patients experienced infection, failure of internal fixation, malunion or other complications in both groups.</div></div><div><h3>Conclusion</h3><div>The results showed that biodegradable high purity Mg screws could be effectively used in the clinical treatment of ankle fractures, ensuring safety and satisfactory postoperative functional recovery.</div><div>The translational potential of this article: The biodegradable high purity Mg screws could provide sufficient mechanical strength and fixation stability for ankle fracture. Our study extended the clinical application of the biodegradable high purity Mg screws for fracture.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"51 ","pages":"Pages 198-206"},"PeriodicalIF":5.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143629178","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}