Journal of Orthopaedic Translation最新文献

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From cells to clinic: Single-cell transcriptomics shaping the future of orthopedics 从细胞到临床:单细胞转录组学塑造骨科的未来
IF 5.9 1区 医学
Journal of Orthopaedic Translation Pub Date : 2025-05-28 DOI: 10.1016/j.jot.2025.05.001
Qiuyuan Wang , Moli Huang , Jiong Jiong Guo
{"title":"From cells to clinic: Single-cell transcriptomics shaping the future of orthopedics","authors":"Qiuyuan Wang ,&nbsp;Moli Huang ,&nbsp;Jiong Jiong Guo","doi":"10.1016/j.jot.2025.05.001","DOIUrl":"10.1016/j.jot.2025.05.001","url":null,"abstract":"<div><div>Single-cell RNA sequencing (scRNA-seq) technology hold significant potential for advancing orthopedic research. This review examines the impact of ScRNA-seq on the future development of orthopedic research and practice. In the study of osteoarthritis, scRNA-seq can finely characterize the changes in the subsets of chondrocytes and their role in disease progression. In rheumatoid arthritis, this technique reveals the complex heterogeneity and cell-to-cell interactions between fibroblasts and immune cells. ScRNA-seq offers insights into the heterogeneity of nucleus pulposus, annulus fibrosus, and endplate cells, providing a novel perspective on the pathological mechanisms of intervertebral disc degeneration. Single-cell analysis in osteosarcoma research has uncovered the complexity of the tumor microenvironment and mechanisms of immunosuppression. Through these studies, scRNA-seq enhances insights into disease pathogenesis and offers innoviate approaches for precision medicine and personalized treatment strategies.</div></div><div><h3>The Translational Potential of this Article</h3><div>This article systematically reviews the cellular heterogeneity, molecular mechanisms and immune microenvironment of orthopedic diseases (such as osteoarthritis, rheumatoid arthritis, intervertebral disc degeneration, osteosarcoma) by single-cell RNA sequencing (scRNA-seq), which provides a theoretical basis for accurate diagnosis, new therapeutic target discovery (such as TRPV1, CXCR4) and individualized treatment strategies. The combination of multi-omics and spatial transcriptome technology is expected to accelerate clinical translation and optimize the diagnosis and treatment system of orthopedic diseases.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"53 ","pages":"Pages 1-11"},"PeriodicalIF":5.9,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mitochondrial Transplantation/Transfer: Promising Therapeutic Strategies for Spinal Cord Injury 线粒体移植/转移:脊髓损伤的治疗策略
IF 5.9 1区 医学
Journal of Orthopaedic Translation Pub Date : 2025-05-01 DOI: 10.1016/j.jot.2025.04.017
Xiaochun Xiong , Chao Zhou , Yijun Yu , Qiong Xie , Linying Xia , Qingping Li , Hongming Lin , Songou Zhang , Wenqing Liang
{"title":"Mitochondrial Transplantation/Transfer: Promising Therapeutic Strategies for Spinal Cord Injury","authors":"Xiaochun Xiong ,&nbsp;Chao Zhou ,&nbsp;Yijun Yu ,&nbsp;Qiong Xie ,&nbsp;Linying Xia ,&nbsp;Qingping Li ,&nbsp;Hongming Lin ,&nbsp;Songou Zhang ,&nbsp;Wenqing Liang","doi":"10.1016/j.jot.2025.04.017","DOIUrl":"10.1016/j.jot.2025.04.017","url":null,"abstract":"<div><div>Spinal cord injury (SCI) remains an unresolved and complex medical challenge. In SCI, mitochondrial dysfunction leads to calcium overload and an increase in reactive oxygen species (ROS). Intercellular mitochondrial transfer has the potential to rescue surviving neurons, while exogenous mitochondrial transplantation can be performed through direct injection or cell-assisted methods. This review explored the current state of research on mitochondrial transplantation and transfer as potential treatments for SCI. It also analyzed the therapeutic implications, influencing factors, and advanced delivery methods for both endogenous mitochondrial transfer and exogenous mitochondrial transplantation. Furthermore, future research directions, including optimizing mitochondrial delivery methods, determining optimal dosages for different delivery approaches, were discussed based on larger animal models and clinical trials. The goal of this review was to introduce novel concepts and prospects for SCI therapy and to contribute to the advancement of medical research in this field.</div></div><div><h3>The Translational Potential of This Article</h3><div>At present, SCI lacks effective therapies, with mitochondrial dysfunction playing a central role in neuronal damage. Mitochondrial transplantation holds promise for restoring bioenergetic function. However, key challenges remain, including optimizing delivery methods, determining appropriate dosages, scalability, donor mitochondrial sourcing, regulatory hurdles and ensuring successful integration. Addressing these issues requires non-invasive platforms, validation in large-animal models, and clinical trials. This approach may bridge mitochondrial biology with translational engineering, thereby advancing the development of regenerative therapies for SCI.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"52 ","pages":"Pages 441-450"},"PeriodicalIF":5.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144071506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Establishment and characterization of an inflammatory cartilaginous organoids model for organoid transplantation study 类器官移植研究中炎性软骨类器官模型的建立与表征
IF 5.9 1区 医学
Journal of Orthopaedic Translation Pub Date : 2025-05-01 DOI: 10.1016/j.jot.2025.05.002
Yanchao Zhang , Qing Fang , Yue Peng , Honglin Liu , Jiancheng Tang , Ruichen Ma , Weiguo Wang
{"title":"Establishment and characterization of an inflammatory cartilaginous organoids model for organoid transplantation study","authors":"Yanchao Zhang ,&nbsp;Qing Fang ,&nbsp;Yue Peng ,&nbsp;Honglin Liu ,&nbsp;Jiancheng Tang ,&nbsp;Ruichen Ma ,&nbsp;Weiguo Wang","doi":"10.1016/j.jot.2025.05.002","DOIUrl":"10.1016/j.jot.2025.05.002","url":null,"abstract":"<div><h3>Background</h3><div>Transplantation of cartilaginous organoids for repairing cartilage defects in osteoarthritis represents a novel treatment approach. However, A controversial argument remains about whether cartilaginous organoids derived from the differentiation of bone marrow mesenchymal stem cells (BMSCs) in the three-dimensional (3D) environment are strictly organoids and whether the inflammatory microenvironment would affect the success rate of organoid transplantation. This study characterized 3D BMSC-derived cartilaginous organoids and developed an inflammatory organoid model to better understand the transcriptomic changes in the organoids induced by the microenvironment when transplanted into the knee with osteoarthritis.</div></div><div><h3>Methods</h3><div>Spatial growth BMSCs were generated and cultured in the cartilage differentiation medium to establish cartilaginous organoids. The model was characterized in both morphology and biology aspects. Subsequently, IL-1β induced inflammatory cartilaginous organoids were established and the transcriptomic sequencing was performed to investigate gene expression changes.</div></div><div><h3>Results</h3><div>BMSC-derived cartilaginous organoids were characterized by histology and immunofluorescence. Both Alcian blue and Safranin O staining revealed abundant articular cartilage extracellular matrix (ECM) in the organoids. The expression of cartilage specific ACAN and Col2A1 was confirmed by immunofluorescence. The organoids had the biological ability to repair cartilage defects. IL-1β induced inflammatory cartilaginous organoids were established and mRNA sequencing revealed downregulation of pathways related to cell adhesion and extracellular matrix organization. Upregulation of IL-6, TNF-α, CCL2 and CXCL1 was confirmed.</div></div><div><h3>Conclusion</h3><div>We thoroughly validated and characterized BMSC-derived cartilaginous organoids and established the inflammatory cartilaginous organoid models. This study revealed that the attenuation in cell adhesion and ECM formation of organoids induced by inflammatory chemokines may decrease the success rate and effectiveness of organoids auto-transplantation for fixing cartilage defects in the inflammatory microenvironment of the OA joint.</div></div><div><h3>The translational potential of this article</h3><div>By establishing and validating an in vitro inflammatory cartilaginous organoid model, this study provides a robust platform to examine how inflammatory mediators influence cartilage-like constructs. These findings enable the identification of targeted interventions to enhance the organoids’ resilience against the inflammatory environment commonly found in osteoarthritic joints. Ultimately, this strategy offers a novel avenue for improving transplant success and promoting cartilage defect repair in patients with OA, thereby contributing valuable insights and potential clinical applications in regenerative medicine.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"52 ","pages":"Pages 376-386"},"PeriodicalIF":5.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143929198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Fibrocartilage hyalinization: A potential therapeutic strategy for articular fibrocartilage 纤维软骨透明化:关节纤维软骨的一种潜在治疗策略
IF 5.9 1区 医学
Journal of Orthopaedic Translation Pub Date : 2025-05-01 DOI: 10.1016/j.jot.2025.04.013
Jiawei Li , Huiming Jiang , Guihua Tan , Zhongyang Lv , Zizheng Liu , Hu Guo , Ziying Sun , Xingquan Xu , Dongquan Shi
{"title":"Fibrocartilage hyalinization: A potential therapeutic strategy for articular fibrocartilage","authors":"Jiawei Li ,&nbsp;Huiming Jiang ,&nbsp;Guihua Tan ,&nbsp;Zhongyang Lv ,&nbsp;Zizheng Liu ,&nbsp;Hu Guo ,&nbsp;Ziying Sun ,&nbsp;Xingquan Xu ,&nbsp;Dongquan Shi","doi":"10.1016/j.jot.2025.04.013","DOIUrl":"10.1016/j.jot.2025.04.013","url":null,"abstract":"<div><div>Articular fibrocartilage is commonly observed on the joint surface in osteoarthritis (OA) or cartilage injury, often seen as a result of cartilage degeneration. Compared to hyaline cartilage, fibrocartilage exhibits inferior mechanical properties and biological functions, which contribute to further cartilage degeneration and the progression of OA. Despite this, research on cartilage regeneration has not sufficiently addressed the specific challenges and strategies related to fibrocartilage. Although fibrocartilage formation is an unavoidable outcome during cartilage repair, it offers several benefits in the regeneration process, such as providing a natural cell source and establishing a strong integration with surrounding tissues. Recently, a therapeutic approach focused on the <em>in-situ</em> modification of fibrocartilage to promote hyaline cartilage regeneration, referred to as “fibrocartilage hyalinization”, has been proposed. Our recent work has demonstrated the feasibility of converting existing fibrocartilage into hyaline cartilage <em>in vivo</em> within the injured area. Key elements of this strategy include modifying the extracellular matrix (ECM), targeting fibrotic chondrocytes, and altering the local microenvironment. This review summarizes the current understanding of articular fibrocartilage's characteristics and mechanisms, while also discussing potential approaches and the feasibility of fibrocartilage hyalinization for cartilage regeneration.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"52 ","pages":"Pages 313-324"},"PeriodicalIF":5.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143902348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
GPX4 activator enhances neuroprotection and functional recovery in spinal cord injury GPX4激活剂增强脊髓损伤的神经保护和功能恢复
IF 5.9 1区 医学
Journal of Orthopaedic Translation Pub Date : 2025-05-01 DOI: 10.1016/j.jot.2025.03.013
Xinjie Liu , Yilin Pang , Baoyou Fan , Jiawei Zhang , Shen Liu , Xiaobing Deng , Yun Li , Ying Liu , Xu Zhang , Chenxi Zhao , Xiaoyu Wang , Xudong Wu , Luhua Lai , Shiqing Feng , Wenpeng Liu , Guangzhi Ning , Xue Yao
{"title":"GPX4 activator enhances neuroprotection and functional recovery in spinal cord injury","authors":"Xinjie Liu ,&nbsp;Yilin Pang ,&nbsp;Baoyou Fan ,&nbsp;Jiawei Zhang ,&nbsp;Shen Liu ,&nbsp;Xiaobing Deng ,&nbsp;Yun Li ,&nbsp;Ying Liu ,&nbsp;Xu Zhang ,&nbsp;Chenxi Zhao ,&nbsp;Xiaoyu Wang ,&nbsp;Xudong Wu ,&nbsp;Luhua Lai ,&nbsp;Shiqing Feng ,&nbsp;Wenpeng Liu ,&nbsp;Guangzhi Ning ,&nbsp;Xue Yao","doi":"10.1016/j.jot.2025.03.013","DOIUrl":"10.1016/j.jot.2025.03.013","url":null,"abstract":"<div><h3>Background</h3><div>Spinal cord injury (SCI) exerts severe physical, social, and economic effects on individuals and the healthcare system. While much progress has been made in understanding the pathophysiology of SCI, the regulation of the ferroptosis master regulator, GPX4 (Glutathione Peroxidase 4), remains poorly understood.</div></div><div><h3>Methods</h3><div>In a rat T10 contusion SCI model, GPX4 expression was tracked with western blot and immunofluorescence. Ferroptosis was induced in primary neurons using the GPX4 inhibitor RSL3, and inflammatory cytokine release was measured. Conditioned media from these neurons was applied to microglia to assess activation. The GPX4 activator PKUMDL-LC-102 was administered to SCI rats, with functional recovery evaluated through behavioral tests, MRI, and motor-evoked potentials.</div></div><div><h3>Results</h3><div>We first reveal a temporal and spatial decrease of GPX4 levels in neurons after SCI. We then demonstrate that GPX4 inhibition leads to primary neuronal ferroptosis, triggering the secretion of pro-inflammatory cytokines that activate microglia. This study represents the initial <em>in vivo</em> investigation of GPX4-specific targeted activation, demonstrating its potential to promote functional recovery in contusive SCI by improving neuronal survival and reducing microgliosis.</div></div><div><h3>Conclusion</h3><div>These findings highlight the significance of GPX4 as a key factor for neuroprotection in the spinal cord. We identified the pivotal role of GPX4 in SCI and realize the neuroprotection via specific GPX4 activation to improve functional recovery <em>in vivo</em>.</div></div><div><h3>The translational potential of this article</h3><div>These findings provide a novel avenue for therapeutic intervention to enhance functional recovery after SCI through GPX4 targeted activation.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"52 ","pages":"Pages 344-359"},"PeriodicalIF":5.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143913044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Sex-dependent variation in bone adaptation: from degeneration to regeneration 骨适应的性别依赖性变异:从退化到再生
IF 5.9 1区 医学
Journal of Orthopaedic Translation Pub Date : 2025-05-01 DOI: 10.1016/j.jot.2025.04.011
Song Chen , Jhanvee Patel , Torey Katzmeyer , Ming Pei
{"title":"Sex-dependent variation in bone adaptation: from degeneration to regeneration","authors":"Song Chen ,&nbsp;Jhanvee Patel ,&nbsp;Torey Katzmeyer ,&nbsp;Ming Pei","doi":"10.1016/j.jot.2025.04.011","DOIUrl":"10.1016/j.jot.2025.04.011","url":null,"abstract":"<div><div>While known sex differences in bone health exist, scientific studies on bone degeneration and regeneration frequently disregard sex impact as a variable in outcomes. Evidence has established a higher risk of osteoporosis and increased bone degradation rates in women when compared to men. Accumulating research suggests that this disparity is also present in bone regeneration and repair. However, no comprehensive review highlighting the influence of sex currently exists in this field. This paper aims to review the information presently available on the cellular mechanisms behind skeletal sexual dimorphism specific to hormones and bone's degenerative and regenerative sex differences. This review will discuss the optimization of personalized regenerative therapies accounting for sex. The review emphasizes that sex impact must further be investigated to advance the field of bone regeneration and improve patient outcomes and quality of life.</div><div>As translational medicine is JOT's focus, authors must highlight the translational potential or clinical significance of their work in both the abstract and the discussion. To this effect, it is required to include a statement following the abstract (included in the abstract word count) under the following heading: \"The Translational Potential of this Article\". 2. Please re-edit the reference list according to the following guidelines: 1) The last names and initials of all the authors up to 6 should be included, but when authors number 7 or more, list the first 6 authors only followed by 'et al'; 2) The \"[eng]\" in the reference list should be removed (if any); 3) Reference to a standard journal article (Please pay particular attention to the formatting, word capitalization, spacing and style): “Niemansburg SL, van Delden JJ, Dhert WJ, Bredenoord AL. Regenerative medicine interventions for orthopedic disorders: ethical issues in the translation into patients. Regen Med 2013;8:65–73.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"52 ","pages":"Pages 325-343"},"PeriodicalIF":5.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143907873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Chk2 deletion rescues bone loss and cellular senescence induced by Bmi1 deficiency via regulation of Cyp1a1 Chk2缺失通过调节Cyp1a1来挽救Bmi1缺乏引起的骨质流失和细胞衰老
IF 5.9 1区 医学
Journal of Orthopaedic Translation Pub Date : 2025-05-01 DOI: 10.1016/j.jot.2025.04.014
Yining Liu , Xiaolei Ji , Jinge Zhang , Jinhong Lu , Boyang Liu , Haijian Sun , Dengshun Miao
{"title":"Chk2 deletion rescues bone loss and cellular senescence induced by Bmi1 deficiency via regulation of Cyp1a1","authors":"Yining Liu ,&nbsp;Xiaolei Ji ,&nbsp;Jinge Zhang ,&nbsp;Jinhong Lu ,&nbsp;Boyang Liu ,&nbsp;Haijian Sun ,&nbsp;Dengshun Miao","doi":"10.1016/j.jot.2025.04.014","DOIUrl":"10.1016/j.jot.2025.04.014","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background/objective&lt;/h3&gt;&lt;div&gt;Bone homeostasis, maintained by a balance between osteoblastic bone formation and osteoclastic bone resorption, is disrupted in osteoporosis, leading to reduced bone mass and increased fracture risk. Bmi1, a polycomb group protein, is crucial for stem cell self-renewal and senescence regulation. Bmi1 deficiency has been linked to oxidative stress, DNA damage, and premature osteoporosis. Checkpoint kinase 2 (Chk2) is a key mediator of the DNA damage response (DDR) pathway, which can exacerbate bone aging through oxidative stress and senescence. This study investigated the role of Chk2 deletion in mitigating bone loss and cellular senescence caused by Bmi1 deficiency and explored the underlying molecular mechanisms, focusing on the regulation of oxidative stress via Cyp1a1.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;We utilized Bmi1-deficient (Bmi1&lt;sup&gt;−/−&lt;/sup&gt;), Chk2-deficient (Chk2&lt;sup&gt;−/−&lt;/sup&gt;), and double knockout (Bmi1&lt;sup&gt;−/−&lt;/sup&gt;Chk2&lt;sup&gt;−/−&lt;/sup&gt;) mice to assess bone homeostasis. Bone mineral density (BMD), trabecular architecture, and bone turnover markers were evaluated using X-ray imaging, micro-CT, histological staining, and bone histomorphometry. Oxidative stress markers, DDR pathway activation, and senescence-associated secretory phenotype (SASP) were analyzed using Western blotting, immunohistochemistry, and real-time PCR. Transcriptome sequencing identified differentially expressed genes, including Cyp1a1, which was further validated through chromatin immunoprecipitation (ChIP), luciferase assays, and knockdown experiments in bone marrow mesenchymal stem cells (BMSCs).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Bmi1 deficiency activated the ATM-Chk2-p53 DDR pathway, increased oxidative stress, and induced osteocyte senescence and senescence-associated secretory phenotype (SASP), leading to reduced osteoblastic bone formation, increased osteoclastic bone resorption, and significant bone loss. Chk2 knockout rescued these defects by reducing oxidative stress and senescence. In Bmi1&lt;sup&gt;−/−&lt;/sup&gt;Chk2&lt;sup&gt;−/−&lt;/sup&gt; mice, BMD, trabecular bone volume, collagen deposition, and osteoblast markers (Runx2 and OPN) were significantly improved, while osteoclast markers (TRAP and RANKL/OPG ratio) were reduced compared to Bmi1&lt;sup&gt;−/−&lt;/sup&gt; mice. Oxidative stress markers, including SOD1 and SOD2, were restored, and senescence markers such as p16, p21, and β-gal activity were significantly decreased. Transcriptome analysis identified Cyp1a1 as a key regulator of oxidative stress downstream of Bmi1 and Chk2. Bmi1 deficiency upregulated Cyp1a1, increasing ROS levels, while Chk2 knockout downregulated Cyp1a1 and mitigated oxidative stress. Mechanistically, p53 was shown to directly bind the Cyp1a1 promoter and activate its transcription, with Chk2 knockout reducing p53-mediated Cyp1a1 expression. These findings highlight the critical role of the Bmi1-Chk2-p53-Cyp1a1 axis in regulating bone homeostasis.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"52 ","pages":"Pages 360-375"},"PeriodicalIF":5.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143929196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Vitamins D and K jointly protect against osteoarthritis via regulating OSCAR during osteoclastogenesis 维生素D和K通过调节破骨细胞生成过程中的OSCAR来共同预防骨关节炎
IF 5.9 1区 医学
Journal of Orthopaedic Translation Pub Date : 2025-05-01 DOI: 10.1016/j.jot.2025.03.018
Yang Zhao , Qianhua Ou , Hong Huang , Delong Li , Jianmao Chen , Song Xue , Zuoqing Zhou , Guangfeng Ruan , Changhai Ding
{"title":"Vitamins D and K jointly protect against osteoarthritis via regulating OSCAR during osteoclastogenesis","authors":"Yang Zhao ,&nbsp;Qianhua Ou ,&nbsp;Hong Huang ,&nbsp;Delong Li ,&nbsp;Jianmao Chen ,&nbsp;Song Xue ,&nbsp;Zuoqing Zhou ,&nbsp;Guangfeng Ruan ,&nbsp;Changhai Ding","doi":"10.1016/j.jot.2025.03.018","DOIUrl":"10.1016/j.jot.2025.03.018","url":null,"abstract":"<div><h3>Objective</h3><div>The effects of vitamins D and K on osteoarthritis (OA) progression remain ambiguous, particularly in its subtype, osteoporotic OA (OPOA), where aberrant activation of osteoclasts exacerbates subchondral bone remodeling. This study aimed to investigate the effect of 1,25-dihydroxyvitamin D3 (calcitriol) and menaquinone-4 (MK4) on OA and OPOA progression and explore their combined mechanisms in osteoclastogenesis inhibition.</div></div><div><h3>Methods</h3><div>Therapeutic effects of calcitriol and MK4 were evaluated in OA and OPOA models induced by medial meniscus destabilization (DMM) and bilateral ovariectomy (OVX). In vitro analyses assessed their impact on chondrocyte degradation and osteoclastogenesis. RNA sequencing of preosteoclasts elucidated the vitamins' anti-osteoclastogenic mechanisms.</div></div><div><h3>Results</h3><div>Combined administration of calcitriol and MK4 significantly attenuated cartilage degradation in OA and OPOA mouse models, though direct effects on chondrocyte degradation were limited. Importantly, calcitriol and MK4 jointly suppressed osteoclastogenesis in vivo and in vitro, ameliorating subchondral remodeling and reducing pain levels in OPOA mice. Mechanistically, osteoclast-associated receptor (OSCAR) mediated their anti-osteoclastogenic effects.</div></div><div><h3>Conclusions</h3><div>Calcitriol and MK4 confer enhanced benefits on OA and OPOA progression through OSCAR-mediated osteoclastogenesis inhibition in preosteoclasts.</div></div><div><h3>The Translational potential of this article</h3><div>This study demonstrates vitamins D and K as dual-action agents inhibiting osteoclastogenesis and normalizing subchondral bone remodeling both in OA and OPOA models, making it a potential therapeutic alternative for the disease.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"52 ","pages":"Pages 387-403"},"PeriodicalIF":5.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Chinese expert consensus on failure and revision after anterior cruciate ligament reconstruction 国内专家对前交叉韧带重建失败与修复的共识
IF 5.9 1区 医学
Journal of Orthopaedic Translation Pub Date : 2025-05-01 DOI: 10.1016/j.jot.2025.03.006
Tianwu Chen , Yongtao Mao , Lunhao Bai , Xizhuang Bai , Qing Bi , Chen Chen , Liaobin Chen , Shiyi Chen , Wai Sin Chan , Guofeng Dai , Xuesong Dai , Lin Guo , Yang Guo , Yaohua He , Ning Hu , Yong Hu , Jingmin Huang , Xuan Huang , Xunwu Huang , Chang-Ming Huang , Jingbin Zhou
{"title":"Chinese expert consensus on failure and revision after anterior cruciate ligament reconstruction","authors":"Tianwu Chen ,&nbsp;Yongtao Mao ,&nbsp;Lunhao Bai ,&nbsp;Xizhuang Bai ,&nbsp;Qing Bi ,&nbsp;Chen Chen ,&nbsp;Liaobin Chen ,&nbsp;Shiyi Chen ,&nbsp;Wai Sin Chan ,&nbsp;Guofeng Dai ,&nbsp;Xuesong Dai ,&nbsp;Lin Guo ,&nbsp;Yang Guo ,&nbsp;Yaohua He ,&nbsp;Ning Hu ,&nbsp;Yong Hu ,&nbsp;Jingmin Huang ,&nbsp;Xuan Huang ,&nbsp;Xunwu Huang ,&nbsp;Chang-Ming Huang ,&nbsp;Jingbin Zhou","doi":"10.1016/j.jot.2025.03.006","DOIUrl":"10.1016/j.jot.2025.03.006","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;With the recent rise in anterior cruciate ligament (ACL) reconstruction surgeries in China, a corresponding increase in surgical failures has been observed. Variability in primary surgical techniques and the intricacies of failure mechanisms have introduced significant challenges in diagnosing failures, planning procedures, and conducting revision surgeries.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;In response to these challenges, the Chinese Association of Orthopaedic Surgeons (CAOS) and the Chinese Society of Sports Medicine (CSSM) initiated the development of an expert consensus on ACL reconstruction failure and revision. Utilizing a modified Delphi method, 67 domestic experts from relevant fields were invited for consensus formulation and review.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;The expert panel achieved a high degree of consensus on twelve key aspects. The consensus clearly defines ACL reconstruction failure and outlines multiple contributing factors, with surgical errors, especially incorrect bone tunnel placement, identified as primary causes. It also emphasizes the significant impact of patient-specific variables on the likelihood of failure. Recommendations for revision surgeries include careful determination of revision indications, preserving meniscal integrity to reduce the risk of joint degeneration, and a preference for single-stage or two-stage surgeries based on individual patient evaluations. A unified approach for managing bone defects remains absent, necessitating comprehensive assessments. Graft selection should be tailored to each patient, with autografts, allografts, or synthetic ligaments as viable options. For patients with a highly positive pivot shift test or those engaged in high-demand athletic activities, anterolateral structure augmentation or reconstruction is recommended.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;The consensus emphasizes the critical need for individualized approaches in ACL revision surgery. By clearly defining failure criteria and outlining strategies for surgical revisions, these statements are expected to serve as a guide for refining clinical practice, reducing complications, and improving surgical outcomes.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;The translational potential of this article&lt;/h3&gt;&lt;div&gt;&lt;ul&gt;&lt;li&gt;&lt;span&gt;1)&lt;/span&gt;&lt;span&gt;&lt;div&gt;&lt;strong&gt;Establishment of Evidence-Based Clinical Guidelines:&lt;/strong&gt; This article presents a rigorously developed expert consensus on ACL reconstruction failure and revision, providing evidence-based clinical guidelines that are directly applicable in surgical practice. The standardization of these protocols across medical institutions has the potential to reduce variability in patient care and improve surgical outcomes on a national scale.&lt;/div&gt;&lt;/span&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;2)&lt;/span&gt;&lt;span&gt;&lt;div&gt;&lt;strong&gt;Advancement of Precision Medicine in ACL Surgery:&lt;/strong&gt; By emphasizing the need for patient-specific approaches in the management of ACL reconstruction failure, t","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"52 ","pages":"Pages 451-463"},"PeriodicalIF":5.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144125004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Solute transport from synovial fluid to articular cartilage and subchondral bone at different stages of osteoarthritis in a live mouse model 骨关节炎不同阶段小鼠活体模型中滑膜液向关节软骨和软骨下骨的溶质转运
IF 5.9 1区 医学
Journal of Orthopaedic Translation Pub Date : 2025-05-01 DOI: 10.1016/j.jot.2025.04.012
Mengcun Chen , Yanmei Yang , Mingshu Cui , Bin Wang
{"title":"Solute transport from synovial fluid to articular cartilage and subchondral bone at different stages of osteoarthritis in a live mouse model","authors":"Mengcun Chen ,&nbsp;Yanmei Yang ,&nbsp;Mingshu Cui ,&nbsp;Bin Wang","doi":"10.1016/j.jot.2025.04.012","DOIUrl":"10.1016/j.jot.2025.04.012","url":null,"abstract":"<div><h3>Objective</h3><div>This study aims to (1) identify a simplified method to preserve sample integrity and maintain original fluorescence distribution; (2) assess the diffusivity of small and large molecules within articular cartilage (AC), calcified cartilage (CC), and subchondral bone (SB); and (3) investigate the changes in solute transport at various stages of osteoarthritis (OA) in a destabilization of the medial meniscus (DMM) murine model.</div></div><div><h3>Methods</h3><div>Fluorescent dyes of small and large molecules were injected into the knee joints of live mice. Joints were harvested and rapidly frozen immediately post-euthanasia. Optimal dye concentrations and dwelling times were determined through exploratory studies. Mice underwent either DMM or sham surgery and were evaluated at 2 and 8 weeks postoperatively. Relative fluorescence intensity was quantified within the AC, CC and SB, complemented by micro-CT, safranin O staining, and collagen II immunohistochemistry staining.</div></div><div><h3>Results</h3><div>The methodology successfully preserved sample integrity and original dye distribution. Fluorescent imaging revealed that small solute was mainly restricted by the tidemark, while large solute showed limited permeability in AC. Permeability of AC remained elevated in the DMM group at both time points. Increased permeability in CC and SB was observed only at 8 weeks post-DMM surgery, accompanied by reduced collagen II amount.</div></div><div><h3>Conclusions</h3><div>In live mice, the tidemark serves as a barrier to small molecule diffusion, while the cartilage surface restricts larger molecules; however, both structures exhibit increased permeability in OA. These findings advance the understanding of OA pathogenesis and suggest potential therapeutic targets related to cartilage permeability.</div></div><div><h3>Translational Potential</h3><div>The findings of this study advance the understanding of osteoarthritis pathogenesis by elucidating the role of solute transport alterations in cartilage and subchondral bone, thereby suggesting potential therapeutic targets aimed at modulating cartilage permeability to improve joint health in osteoarthritis.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"52 ","pages":"Pages 291-300"},"PeriodicalIF":5.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143898472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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