Journal of Orthopaedic Translation最新文献

{"title":"Deciphering inter-organ communication: The multi-organ-bone axis in osteoporosis and emerging therapeutic strategies","authors":"Ruiming Wen , Haixia Wang , Songtao Wang","doi":"10.1016/j.jot.2026.101119","DOIUrl":"10.1016/j.jot.2026.101119","url":null,"abstract":"<div><h3>Background</h3><div>Osteoporosis has long been considered a disorder confined to bone tissue. Growing evidence now highlights its systemic origins, governed by intricate communication between multiple organs. The multi-organ-bone axis (MOBA) reframes osteoporosis pathogenesis as disrupted communication between bone and peripheral organs. Although dysfunction in organs such as the gut, adipose tissue, and nervous system has been linked to bone loss, a comprehensive integration of this axis and its therapeutic implications remain incomplete. Clarifying this multi-organ network is essential for devising innovative systemic treatment strategies.</div></div><div><h3>Methods</h3><div>This review synthesizes current evidence on the MOBA by conducting a comprehensive literature search in PubMed and Web of Science from inception up to March 2025. Search terms included combinations of “osteoporosis,” “multi-organ bone axis,” “gut-bone axis,” “adipose-bone axis,” “neuro-bone axis,” “kidney-bone axis,” “muscle-bone axis,” “probiotics,” “prebiotics,” “natural products,” “small molecule inhibitors,” and “exercise.” Eligible studies included original research articles, clinical trials, and high-quality reviews published in English that addressed inter-organ communication in bone metabolism.</div></div><div><h3>Results</h3><div>The MOBA framework indicates that bone homeostasis is governed by dynamic interactions among the gut, adipose tissue, nervous system, kidney and skeletal muscle. Dysfunction in these organs perturbs hormonal, inflammatory, immune and neural signaling, thereby driving bone loss through convergent mechanisms. On the basis of this framework, emerging therapeutic strategies can be grouped into five categories: microbiota-directed interventions, natural products, small-molecule inhibitors or agonists, synthetic compounds and exercise. Rather than acting exclusively on bone cells, these approaches aim to restore systemic homeostasis by reprogramming organ crosstalk.</div></div><div><h3>Conclusions</h3><div>The MOBA model offers an integrative framework that conceptualizes osteoporosis as a systemic disorder involving disrupted inter-organ communication. While axis-targeted interventions show preclinical promise, their clinical translation is challenged by mechanistic complexity, model limitations, and insufficient clinical validation. Future research should map precise inter-organ circuits in humans and validate these strategies in patient populations to advance the development of effective systemic osteoporosis therapies.</div></div><div><h3>The translational potential of this article is as follows</h3><div>This Review positions osteoporosis as a systemic disease driven by disordered inter-organ communication. By outlining the MOBA framework and classifying emerging multi-organ-targeted interventions, it shifts the therapeutic focus from bone-centred treatment to system-level recalibration, offering a conceptual basis for more effecti","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"58 ","pages":"Article 101119"},"PeriodicalIF":5.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147802900","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}

{"title":"Myotendinous Junction development and repair","authors":"Kun Yang ,&nbsp;Zi Yin ,&nbsp;Chunmei Fan","doi":"10.1016/j.jot.2026.101097","DOIUrl":"10.1016/j.jot.2026.101097","url":null,"abstract":"<div><div>The myotendinous junction (MTJ) is the critical interface connecting muscle to tendon, enabling force transmission for movement and serving as the primary site of muscle injuries. Despite research into MTJ repair, treatment outcomes are suboptimal, partly due to the absence of a comprehensive synthesis of its structural components, cellular diversity, and developmental mechanisms, which impedes the rational selection of materials, cells, and regulatory factors for effective regeneration. This review synthesizes current knowledge on the cytoskeletal and extracellular matrix (ECM) architecture of the MTJ, the cell types involved in its development and repair, and the key molecular regulators governing its formation. We describe the hierarchical architecture of the MTJ and the key molecular complexes that mediate the mechanical connection between the muscle and the tendon. We also describe the roles of Col22a1-expressing muscle nuclei and various resident stem/progenitor cells in MTJ maintenance and healing. We discuss essential regulatory signaling pathways, including Slit, LRT, and BMP4. Furthermore, we evaluate existing MTJ repair strategies. Based on a review of MTJ development and injury repair, we observe that current treatment approaches largely fail to incorporate key insights from MTJ development, particularly regarding stem/progenitor cells and regulatory signals. Therefore, we propose that tissue engineering techniques, by integrating MTJ-resident stem/progenitor cells such as CD106⁺CD24⁻muscle-tendon progenitors (MTPs) and Hic1⁺Col22a1⁺ progenitors, key MTJ developmental regulatory signals like Slit, Lrt, and BMP4, as well as MTJ decellularized ECM scaffolds or biomimetic 3D-printed scaffolds, will substantially enhance the efficacy of MTJ repair therapies.</div></div><div><h3>The Translational Potential of this Article</h3><div>This review summarizes MTJ development across molecular linkages, signaling regulation, cellular composition, and tissue architecture, while assessing MTJ injury repair in terms of efficacy, mechanisms, limitations, and translational paths. Key barriers of MTJ repair include: conventional treatments (conservative and surgical) lacking high-quality data, RCTs, and unified guidelines for diverse patients; emerging approaches (bioactive factors, cell therapies, decellularized ECM scaffolds, tissue engineering) stuck at proof-of-concept or small-animal stages, without large-animal validation. It proposes establishing standardized cohorts, protocols, and parameters for conventional methods; accelerating large-animal safety/efficacy testing for emerging approaches to speed translation; constructing MTJ organoids based on key developmental cells and cues to provide a rapid drug testing platform for MTJ injury, thereby accelerating clinical translation; and integrating MTJ regulatory signals and stem/progenitor cells to enhance emerging therapy outcomes.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"58 ","pages":"Article 101097"},"PeriodicalIF":5.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147803446","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}

{"title":"Endothelin-1/endothelin B receptor signalling mediates Prx1+ skeletal stem cells senescence: A driver of osteoporotic bone loss","authors":"Zhou Zou ,&nbsp;Weiyuan Gong ,&nbsp;Xuan Lu ,&nbsp;Yuqi Zhang ,&nbsp;Manting Au ,&nbsp;Junxin Lin ,&nbsp;Hongwei Ouyang ,&nbsp;Guozhi Xiao ,&nbsp;Bin Tang ,&nbsp;Chunyi Wen","doi":"10.1016/j.jot.2026.101048","DOIUrl":"10.1016/j.jot.2026.101048","url":null,"abstract":"<div><h3>Background</h3><div>Stem cells residing in the perivascular niche are critical for skeletal homeostasis. Vascular endothelin-1 (ET-1) controls stem cell fate in development, but its role in the exhaustion of skeletal stem cells (SSCs) and subsequent bone degeneration in osteoporosis remains poorly understood. This study aimed to determine whether ET-1 signalling drives SSCs senescence and to elucidate the underlying mechanisms.</div></div><div><h3>Methods</h3><div>We utilised a combination of human single-cell RNA sequencing datasets, murine models of ageing and ovariectomy (OVX), and an endothelial-specific ET-1 overexpression transgenic (TET-1) mouse model. <em>In vitro</em> studies on mesenchymal stem cells (MSCs) employed ET-1 challenge with and without receptor-specific antagonists (BQ123 for ET_AR, BQ788 for ET_BR). The mechanism was further probed using transcriptomic profiling and validated <em>in vivo</em> through Prx1⁺ SSCs-specific ET_BR knockout (Prx1-Cre;ET_BR^{<em>fl/fl</em>}) and pharmacological inhibition with the ET_BR antagonist BQ788.</div></div><div><h3>Results</h3><div>In aged and OVX mice, ET_BR expression was significantly upregulated in SSCs concurrent with bone loss. Transgenic ET-1 overexpression recapitulated an aged bone phenotype, inducing SSCs senescence and accelerating bone loss. <em>In vitro</em>, ET-1 triggered MSCs senescence and reactive oxygen species (ROS) accumulation. Such effects were specifically abrogated by ET_BR, but not ET_AR. Transcriptomic analysis revealed that ET-1/ET_BR signalling synergistically dysregulates the PI3K-AKT and p53 pathways to orchestrate senescence. Critically, both genetic knockout of ET_BR in Prx1⁺ SSCs and pharmacological inhibition with BQ788 mitigated oxidative stress, reduced cellular senescence, and preserved bone mass in OVX and aged mice.</div></div><div><h3>Conclusion</h3><div>This study identified the ET-1/ET_BR signalling axis as a critical driver of osteoporosis by promoting ROS-mediated SSCs senescence. We established a link between vascular ageing and skeletal decline.</div></div><div><h3>The translational potential of this article</h3><div>This study positioned ET_BR blockade as a promising novel therapeutic strategy for osteoporosis. By targeting the upstream driver of SSCs exhaustion, ET_BR inhibition offers a potential paradigm shift from palliative care to proactive rejuvenation of the osteogenic niche. This approach could counteract both postmenopausal and age-related bone loss by restoring the bone-forming potential of the skeleton, addressing a significant unmet clinical need.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"57 ","pages":"Article 101048"},"PeriodicalIF":5.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147306965","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}

{"title":"Medical large language models and systems in the clinical application of spinal diseases: Current status, challenges, and future prospects","authors":"Wenyan Tang ,&nbsp;Ruizhi Chen ,&nbsp;Xiao Long ,&nbsp;Dongdong Yu ,&nbsp;Shen Zhao ,&nbsp;Bin Chen","doi":"10.1016/j.jot.2026.101050","DOIUrl":"10.1016/j.jot.2026.101050","url":null,"abstract":"<div><div>Large Language Models (LLMs), represented by the Generative Pretrained Transformer (GPT), are profoundly transforming the healthcare sector. Spine medicine, a discipline heavily reliant on complex imaging data, detailed clinical records, and evidence-based medical practice, serves as an ideal testing ground for exploring and applying these advanced artificial intelligence technologies. It holds the promise of optimizing clinical workflows, enhancing the quality of diagnosis and treatment decisions, and improving patient communication.</div><div>We systematically searched PubMed and Embase from January 2023 to September 2025 for studies investigating LLMs in spinal diseases. Original research articles published in English with a Journal Impact Factor (JIF) ≥ 3.0 were included. Reviews, case reports, animal studies, and non-orthopedic topics were excluded. Data from eligible studies were extracted and narratively synthesized.</div><div>This review aims to systematically and comprehensively examine the current state of clinical applications of medical large models and related intelligent systems in the field of spinal diseases. The focus is on analyzing their core technical pathways, specific clinical application scenarios, and their medical value, and performance evaluation results, thereby identifying current opportunities and key challenges. Furthermore, it anticipates future developments, from leveraging general-purpose models to constructing specialized models based on high-quality, large-scale, multimodal spine-specific datasets.</div><div><em>The translational potential of this article</em>: The translational potential of this article lies in its provision of a comprehensive roadmap and practical framework for implementing artificial intelligence in spinal surgery. It systematically synthesizes core application scenarios for large language models—including clinical documentation assistance and preoperative planning—while explicitly addressing four critical challenges requiring resolution for successful clinical integration: regulatory compliance, data privacy protection, algorithmic bias mitigation, and workflow integration. It establishes an actionable foundation for collaborative efforts among clinicians, developers, and policymakers to deploy safe, effective, and compliant AI tools in spinal care.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"57 ","pages":"Article 101050"},"PeriodicalIF":5.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147284157","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}

{"title":"A novel multimodal AI-based radiomics approach for precision assessment of pain intensity in chronic nonspecific low back pain","authors":"Moran Suo ,&nbsp;Changjun Ma ,&nbsp;Xin Chen ,&nbsp;Yu Guan ,&nbsp;Xiulin Wang ,&nbsp;Zhonghai Li","doi":"10.1016/j.jot.2026.101062","DOIUrl":"10.1016/j.jot.2026.101062","url":null,"abstract":"<div><h3>Background</h3><div>Chronic nonspecific low back pain (cNLBP) is a prevalent global health concern. Radiomics enables the extraction of high-dimensional quantitative features from medical images and has shown promise in disease diagnosis, prognostic assessment, and therapeutic response evaluation. To construct and validate an artificial intelligence (AI)-based evaluation model for clinical symptoms in cNLBP patients, leveraging both clinical and radiomics features. The clinical utility of this approach was evaluated in identifying patients at high risk for severe pain.</div></div><div><h3>Methods</h3><div>A total of 148 patients with cNLBP were enrolled and stratified by VAS into mild and severe pain groups. Radiomics features from the paraspinal muscles were extracted from lumbar MRI scans. Multiple AI algorithms were applied to construct evaluation models. Logistic regression was used to construct clinical models, radiomics models, and combined clinical - radiomics models, respectively, to compare the predictive power of different models. Model performance was evaluated by multiple methods.</div></div><div><h3>Results</h3><div>Fat infiltration rate of multifidus muscles as significant predictors of pain intensity. The Bagging decision tree model and random forest model achieved higher area under the ROC curve (AUC) values and F1 scores, respectively, in radiomics models. The combined models integrating radiomics and clinical features further increased AUCs.</div></div><div><h3>Conclusion</h3><div>AI algorithms have a significant advantage over traditional algorithms in improving the performance of predictive models. Integrating radiomics features with clinical variables significantly enhances the predictive performance for pain intensity in cNLBP. Multimodal data integration compensates for the limitations of single-modality models, improving both accuracy and stability.</div></div><div><h3>The translational potential of this article</h3><div>This study facilitates early risk stratification of cNLBP patients in clinical practice, enabling clinicians to prioritize intervention for high-risk individuals and optimize the allocation of medical resources. Moreover, the validated high-performance AI models and the multimodal integration strategy lay a foundation for the development of clinical auxiliary tools. Such tools can be integrated into existing clinical workflows to assist clinicians in accurately identifying patients with severe pain at high risk, thereby supporting early intervention and personalized treatment decision-making.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"57 ","pages":"Article 101062"},"PeriodicalIF":5.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147377825","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}

{"title":"Proteomic biomarkers in rotator cuff disease: Current evidence and translational implications from a systematic review and network analysis","authors":"Elvira Immacolata Parrotta ,&nbsp;Giorgia Lucia Benedetto ,&nbsp;Giovanni Cuda ,&nbsp;Raffaele Covello ,&nbsp;Umile Giuseppe Longo ,&nbsp;Arianna Carnevale ,&nbsp;Olimpio Galasso ,&nbsp;Giorgio Gasparini ,&nbsp;Michele Mercurio","doi":"10.1016/j.jot.2026.101069","DOIUrl":"10.1016/j.jot.2026.101069","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Rotator cuff disorders are among the most common causes of shoulder pain and dysfunction, primarily driven by chronic inflammation and degenerative changes in tendon tissue. These alterations lead to progressive structural damage and compromised function. In recent years, proteomic profiling has emerged as a promising strategy for identifying molecular signatures associated with disease mechanisms and potential translational applications.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;A systematic review was conducted using PubMed and Scopus databases, targeting studies published between 2015 and 2024. Included studies focused on proteomic biomarker analysis in synovial fluid, and blood from patients affected by rotator cuff disorders. Methodological quality and risk of bias were evaluated using the Newcastle-Ottawa Scale for observational studies and the RoB 2.0 tool for randomized controlled trials.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Seven studies were found to meet the inclusion criteria. Among the most consistently reported proteins were matrix metalloproteinase-1, matrix metalloproteinase-13, interleukin-1β, interleukin-6, and transforming growth factor-β1, with a predominant presence in synovial fluid samples. Enrichment analyses pointed to their involvement in inflammatory cascades, extracellular matrix turnover, and neovascularization. Network analysis of protein-protein interactions highlighted interleukin-6 and matrix metalloproteinase-13 as central nodes, indicating a pivotal role in modulating disease progression.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;The most reported biomarkers, such as matrix metalloproteinase-1, matrix metalloproteinase-13, interleukin-1&lt;strong&gt;β&lt;/strong&gt;, interleukin-6, and transforming growth factor-&lt;strong&gt;β&lt;/strong&gt;1, are associated primarily with inflammatory signaling and extracellular matrix remodeling, highlighting their involvement in molecular pathways related to rotator cuff disease progression and tissue degeneration. Gene Ontology enrichment and KEGG pathway analyses further revealed that these proteins are significantly involved in biological processes relevant to tendon degeneration, including cytokine-mediated signaling, the wound response, and ECM organization.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Clinical implications&lt;/h3&gt;&lt;div&gt;The identified biomarkers, particularly interleukin-6, matrix metalloproteinase-1, matrix metalloproteinase-13, and transforming growth factor-β1, may represent candidates for inclusion in future multi-analyte diagnostic panels, pending rigorous clinical validation. However, at present these applications remain hypothetical. Further large-scale, standardized, and longitudinal studies are required to validate their incremental value beyond imaging and clinical evaluation before any clinical translation can be considered.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;The translational potential of this article&lt;/h3&gt;&lt;div&gt;This systematic review synthesizes current evidence on proteomic biomarkers ","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"57 ","pages":"Article 101069"},"PeriodicalIF":5.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147540219","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}

{"title":"Engineering multifunctional microspheres for sequential regulation of osteoimmune microenvironment and bone remodeling balance to promote regeneration of osteoporotic bone defects","authors":"Zhiheng Luo ,&nbsp;Jianxiong Ma ,&nbsp;Yipei Yang ,&nbsp;HongJie Zhang ,&nbsp;Yuhan Du ,&nbsp;Jing Dai ,&nbsp;Yan Wang ,&nbsp;Wei Zhang ,&nbsp;Xinlong Ma ,&nbsp;Yuxiao Lai","doi":"10.1016/j.jot.2026.101054","DOIUrl":"10.1016/j.jot.2026.101054","url":null,"abstract":"<div><h3>Objectives</h3><div>Osteoporotic bone defect repair remains clinically challenging due to persistent low-grade inflammation, excessive reactive oxygen species (ROS), and dysregulated bone metabolism. Approaches relying solely on osteoclast inhibition are often insufficient, particularly for irregular osteoporotic bone voids. This study aimed to develop a multifunctional microsphere system capable of sequential osteoimmune regulation and bone metabolic remodeling.</div></div><div><h3>Methods</h3><div>Gelatin microspheres grafted with alendronate and loaded with epigallocatechin gallate (Gel@ALN@E) were fabricated via an emulsion–chemical crosslinking method to enable controlled dual-drug release. In <em>vitro</em> evaluations included ROS scavenging, inflammatory modulation, macrophage polarization, osteoclast differentiation, and osteogenic responses of rat bone marrow mesenchymal stem cells. Transcriptomic analysis was conducted to investigate immunoregulatory mechanisms. An osteoporotic rat bone defect model was used for in <em>vivo</em> assessment.</div></div><div><h3>Results</h3><div>Gel@ALN@E effectively reduced oxidative stress and inflammatory responses by promoting macrophage M2 polarization, while concurrently suppressing osteoclastogenesis and restoring bone metabolic balance. This coordinated regulation significantly enhanced osteogenic differentiation. Transcriptomic analysis revealed the downregulation of related inflammatory pathways. In <em>vivo</em>, Gel@ALN@E markedly improved new bone formation, trabecular organisation, and cortical bone healing in osteoporotic defects.</div></div><div><h3>Conclusion</h3><div>This sequential drug release system offers a promising platform for both immunomodulation and bone regeneration in osteoporotic defect repair.</div></div><div><h3>The Translational Potential of this Article</h3><div>The composite engineered microsphere system Gel@ALN@E integrates local immunomodulatory and osteoclast-inhibitory functions to directly address key pathological microenvironmental features of osteoporotic bone defects. This integrative design highlights its comprehensive pro-regenerative capacity and provides support for its translational application in the clinical treatment of irregular osteoporotic bone defects.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"57 ","pages":"Article 101054"},"PeriodicalIF":5.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147425003","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}

{"title":"Magnesium ions facilitate osteogenic differentiation and intervertebral fusion via m6A methylation of RhoA mRNA","authors":"Haocheng Xu ,&nbsp;Linli Li ,&nbsp;Fan Zhang ,&nbsp;Minghao Shao ,&nbsp;Chenyan Li ,&nbsp;Yitong Xue ,&nbsp;Dachuan Li ,&nbsp;Zhidi Lin ,&nbsp;Zhaoyang Gong ,&nbsp;Jiongdong Wu ,&nbsp;Zhiwen Luo ,&nbsp;Zhicai Shi ,&nbsp;Xinlei Xia ,&nbsp;Hongli Wang ,&nbsp;Xiaosheng Ma ,&nbsp;Jianyuan Jiang ,&nbsp;Xiaochuan Gu ,&nbsp;Yang Liu ,&nbsp;Xiao Lu ,&nbsp;Feizhou Lyu","doi":"10.1016/j.jot.2026.101056","DOIUrl":"10.1016/j.jot.2026.101056","url":null,"abstract":"<div><h3>Background</h3><div>Magnesium-based implants facilitate bone regeneration <em>via</em> degradation. However, the epigenetic mechanisms, particularly N6-methyladenosine (m6A) modification regulated by Mg²⁺, remain incompletely understood. This study investigated the role of Mg²⁺ in osteogenic differentiation through the METTL3-RhoA axis and evaluated its potential in intervertebral fusion.</div></div><div><h3>Methods</h3><div>The optimal Mg²⁺ concentration was identified using MC3T3-E1 cells. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and MeRIP-PCR were employed to identify m6A target genes. Functional assays (knockdown, overexpression, and rescue) validated the METTL3-YTHDF1-RhoA pathway. A rat tail intervertebral fusion model with magnesium implants was used to assess <em>in vivo</em> effects.</div></div><div><h3>Results</h3><div>Treatment with 4 mM Mg²⁺ significantly enhanced osteogenic activity and increased METTL3 levels. Mechanistically, METTL3 promoted m6A methylation of RhoA mRNA, which was subsequently bound by YTHDF1, enhancing translation and activating the RhoA/ROCK pathway. <em>In vivo</em>, magnesium implants accelerated fusion and improved trabecular bone quality; however, these effects were inhibited by METTL3 or RhoA inhibitors.</div></div><div><h3>Conclusion</h3><div>Mg²⁺ enhances osteogenic differentiation through the METTL3-YTHDF1-RhoA/ROCK pathway.</div></div><div><h3>The translational potential of this article</h3><div>This study provides an epigenetic framework for optimizing magnesium-based orthopedic implants and suggests that targeting the m6A-RhoA axis could improve spinal fusion outcomes.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"57 ","pages":"Article 101056"},"PeriodicalIF":5.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147307014","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}

{"title":"Foot and ankle biomaterials: a comprehensive review of current applications, challenges, and future directions","authors":"Peter Elvin ,&nbsp;Amayrani Sanchez ,&nbsp;Anthony Allen Reyes ,&nbsp;Hagner Andrade ,&nbsp;Meelad Karami ,&nbsp;Hooman T. Mir ,&nbsp;Javier La Fontaine ,&nbsp;Danieli C Rodrigues ,&nbsp;Claudia Biguetti","doi":"10.1016/j.jot.2026.101051","DOIUrl":"10.1016/j.jot.2026.101051","url":null,"abstract":"<div><div>Metallic biomaterials enable successful reconstruction and fixation of skeletal tissues by supporting repair, load-bearing function, and anatomical alignment in foot and ankle surgery. However, the unique anatomic and biomechanical demands of this region, combined with challenging pathologies such as flatfoot and Charcot neuroarthropathy, present distinct challenges, with effective intervention requiring targeted biomaterial solutions and precise indications. Furthermore, metallic biomaterials currently represent the most predominant and clinically validated fixation systems in foot and ankle surgical reconstructions, while also generating the largest body of outcome-based evidence. This review summarizes and discusses their contemporary applications, outcomes, limitations, unmeet needs, and future directions based on clinical literature between 2020 and 2024. Emerging innovations, including 3D-printed titanium implants for patient-specific reconstructions, surface-engineered alloys designed to improve osseointegration, with infection mitigation properties for at risk patient populations, and the exploration of bioresorbable/biointegrative magnesium, as well as non-metallic alternative materials (e.g. polymerics) were examined. Persistent unmet needs identified in the literature include hardware challenges in osteoporotic bone and neuropathic patients, ion leeching, cyclic fatigue, economic burden, imaging artifact interference, and lack of long-term data or clinical trials on innovative implant designs and manufacturing approaches. Lastly, scanning electron microscopy (SEM) imaging of titanium, nitinol, and stainless steel is provided to offer an analysis on biomaterial-specific microstructural features, such as surface roughness and porosity, that play a role in influencing tissue integration, corrosion behavior, and mechanical performance in reconstructive surgeries. The Translational Potential of this Article: This review provides clinically actionable guidance for selecting metallic biomaterials tailored to the biomechanical and pathological demands of foot and ankle surgery, supporting evidence-based decisions of selection of hardwares, improved fixation strategies, and reduced complication rates. It also adds recent insights to inform the development and optimization of next-generation devices based on patient- and site-specific requirements, such as 3D-printed constructs and surface-engineered implants, designed to enhance fusion, reconstruction, and limb salvage outcomes.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"57 ","pages":"Article 101051"},"PeriodicalIF":5.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147348560","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}

{"title":"LBX1 alters polyamine pathway in adolescent idiopathic scoliosis – a new therapeutic target to mitigate curve progression","authors":"Zhe Zhang ,&nbsp;Yujia Wang ,&nbsp;Zongshan Hu ,&nbsp;Wenlin Tian ,&nbsp;Mengheng Li ,&nbsp;Ziyang Tang ,&nbsp;Liang Chang ,&nbsp;Hok-him Tang ,&nbsp;Gen Tang ,&nbsp;Jie Li ,&nbsp;Zhichong Wu ,&nbsp;Haixia Xu ,&nbsp;Elvis Chun-sing Chui ,&nbsp;Zhen Liu ,&nbsp;Adam Yiu-chung Lau ,&nbsp;Tsz-ping Lam ,&nbsp;Daniel Kam-wah Mok ,&nbsp;Huanxiong Chen ,&nbsp;Yong Qiu ,&nbsp;Jack Chun-Yiu Cheng ,&nbsp;Wayne Yuk-Wai Lee","doi":"10.1016/j.jot.2026.101063","DOIUrl":"10.1016/j.jot.2026.101063","url":null,"abstract":"<div><h3>Background</h3><div>Adolescent idiopathic scoliosis (AIS) is the most common three-dimensional (3D) spinal deformity occurring during puberty, with girls at a higher risk of curve progression to the surgical threshold. Ladybird homeobox 1 (LBX1) is the most promising AIS predisposing gene based on GWAS studies, but its role in curve progression remains elusive.</div></div><div><h3>Methods</h3><div>The role of LBX1 in muscle phenotype and curve progression was investigated in clinical samples and mouse models. Additionally, metabolomic analysis was used to explore signaling pathway and potential therapeutic target.</div></div><div><h3>Results</h3><div>In this study, we found elevated <em>LBX1</em> and myogenic genes expression, along with increased proportion of type I muscle fibers, in the convex paraspinal muscle (PSM) of AIS patients. Notably, the concave/convex <em>LBX1</em> ratio in PSM negatively correlates with curve severity. Using a 3D-printed asymmetric hypokyphosing thoracic restrainer, we established AIS-like 3D spinal deformities in young female mice, consistently inducing a thoracic right curve. AAV-mediated Lbx1 knockdown in concave PSM of Lbx1^fl/fl mice exacerbated curve progression by 50%. Mechanistically, Lbx1 knockdown inhibited myogenesis and muscle regeneration, and altered polyamine synthesis pathway. Key polyamine pathway enzymes ODC1 and SAT1 were reduced in concave PSM of AIS patients. The resultant lower serum level of spermidine, a key polyamine metabolite, was found in progressive AIS patients at their initial clinical visits. Importantly, daily spermidine supplementation significantly mitigated curve progression in scoliosis-like mice.</div></div><div><h3>Conclusion</h3><div>Our findings provide new evidence that differential Lbx1 expression in bilateral PSM exacerbates curve progression. The associated altered polyamine pathway and reduced circulating spermidine level represent novel therapeutic target and prognostic biomarker, respectively.</div></div><div><h3>The translational potential of this article</h3><div>This study presents a straightforward and reproducible protocol for establishing a mouse model of spinal deformity with consistent curvature pattern for AIS research, and illustrates the potential role of the LBX1-mediated polyamine pathway in driving curve progression in AIS, which can be ameliorated by oral spermidine administration. Our findings highlight the modulation of paraspinal muscles as a viable approach to halting curve progression.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"57 ","pages":"Article 101063"},"PeriodicalIF":5.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147425023","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}