Journal of Orthopaedic Translation最新文献

{"title":"Efficacy of once-weekly teriparatide versus alendronate in Chinese postmenopausal osteoporosis: a randomised, open-label, active-controlled, 48-week, multicentre phase III study","authors":"Jiemei Gu ,&nbsp;Aijun Chao ,&nbsp;Yanan Huo ,&nbsp;Yawei Zhang ,&nbsp;Zhong Yuan ,&nbsp;Jun Zhang ,&nbsp;Zhifeng Cheng ,&nbsp;Li Mao ,&nbsp;Yukun Li ,&nbsp;Qingyun Xue ,&nbsp;Feng Liu ,&nbsp;Yuhong Zeng ,&nbsp;Yikun Zhu ,&nbsp;Mengmeng Zhang ,&nbsp;Liping Li ,&nbsp;Lijun Liu ,&nbsp;Fei Gao ,&nbsp;Qun Cheng ,&nbsp;Xieyuan Jiang ,&nbsp;Chen Wang ,&nbsp;Zhenlin Zhang","doi":"10.1016/j.jot.2026.101101","DOIUrl":"10.1016/j.jot.2026.101101","url":null,"abstract":"<div><h3>Objectives</h3><div>This randomised controlled trial assessed the effectiveness and safety of weekly 56.5 μg teriparatide (SAL056) compared to alendronate in postmenopausal women in China with osteoporosis at high risk of fractures over 48 weeks.</div></div><div><h3>Methods</h3><div>This phase 3, multicentre, randomised, open-label, active-controlled, parallel-group, non-inferiority trial enrolled postmenopausal women aged 45–80 years with osteoporosis at 37 centres in China. Participants were randomised (1:1) to receive either subcutaneous teriparatide 56.5 μg weekly or 70 mg oral alendronate weekly for 48 weeks, with the primary efficacy assessment at Week 48.</div></div><div><h3>Results</h3><div>Between November 2021 and September 2023, 493 patients were enrolled (243 in the teriparatide group and 250 in the alendronate group). The primary endpoint, lumbar spine bone mineral density (BMD) at L1–L4, showed a significantly greater increase in the teriparatide group compared to the alendronate group at Week 48 (5.01% vs. 4.20%, mean difference 0.80%, <em>P</em> = 0.025). Sensitivity analysis confirmed these results. At Weeks 24 and 48, teriparatide also resulted in higher hip BMD than alendronate (1.50% vs. 1.46%, <em>P</em> &gt; 0.05 and 3.27% vs. 1.67%, <em>P</em> &lt; 0.001). Procollagen type 1 N-terminal propeptide (P1NP) levels in the teriparatide group increased transiently at Week 12, then declined toward baseline by Weeks 24 and 48, and a decrease in serum cross-linked c-terminal telopeptide of type I collagen (S-CTX) levels from baseline to the end of treatment. Meanwhile, in the alendronate (a typical bone resorption inhibitor) group, CTX level remained continuously suppressed from the baseline. Clinical fracture rates were lower in the teriparatide group than in the alendronate group at Weeks 24 (1.2% vs. 2.8%, <em>P</em> &gt; 0.05) and 48 (1.7% vs. 4.0%, <em>P</em> &gt; 0.05). Teriparatide was generally safe and well tolerated.</div></div><div><h3>Conclusions</h3><div>Teriparatide (56.5 μg once weekly) was more effective than alendronate in treating postmenopausal osteoporosis with a high fracture risk, significantly increasing L1–L4 BMD over 48 weeks. It was safe, well tolerated, and had a safety profile similar to that of Teribone®.</div></div><div><h3>The translational potential of this article</h3><div>This study demonstrates that once-weekly teriparatide significantly improves bone mineral density and reduces fracture risk in postmenopausal osteoporosis patients. As a patient-friendly alternative to daily injections, it may enhance adherence and inform clinical guidelines, representing a promising strategy for patients and healthcare systems.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"58 ","pages":"Article 101101"},"PeriodicalIF":5.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147951588","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":"Type E endothelial cells orchestrate embryonic skeletogenesis via chondrogenic priming of skeletal progenitors","authors":"Yang-Yang Li ,&nbsp;Sha Huang ,&nbsp;Ou Hu ,&nbsp;Qin Qin ,&nbsp;Pulin Yan ,&nbsp;Peng Lin ,&nbsp;Ying-Bo Wang ,&nbsp;Huai-Jian Jin ,&nbsp;Jian Wu ,&nbsp;Yu-Tong Wu ,&nbsp;Na Luo ,&nbsp;Qing-Hua Ma ,&nbsp;Rui-Li Cai ,&nbsp;Yang-Li Xie ,&nbsp;Lin Chen ,&nbsp;Yi-Bo Gan ,&nbsp;Peng Liu ,&nbsp;Jian He","doi":"10.1016/j.jot.2026.101123","DOIUrl":"10.1016/j.jot.2026.101123","url":null,"abstract":"<div><h3>Background</h3><div>Skeletal stem/progenitor cells (SSPCs) are pivotal orchestrators of embryonic skeletogenesis, underlying chondrogenesis and osteogenesis, however, the molecular determinants governing SSPC functionality remain elusive.</div></div><div><h3>Methods</h3><div>We performed single-cell RNA sequencing (scRNA-seq) to delineate cellular heterogeneity within the developing limb bud and to identify candidate cellular markers. The spatiotemporal distribution of target cell populations was further examined via immunofluorescence staining. Fluorescence-activated cell sorting (FACS) was used to isolate endothelial cells and SSPCs based on surface markers. Functional properties of these cells were assessed using in vitro assays, and direct co-culture experiments were conducted to evaluate intercellular communication and underlying molecular pathways.</div></div><div><h3>Results</h3><div>We delineate a CD140a ⁺ PDPN ⁺ SSPC population characterized by robust self-renewal and multipotency, peaking in abundance at embryonic day 14.5. Concomitantly, we resolved the heterogeneity within endothelial cell (EC) populations during embryonic angiogenesis, identifying a distinct subpopulation exhibiting high Pecam1 and low Emcn expression (recapitulating type E). Critically, SSPCs manifested enhanced chondrogenic differentiation potential and type II collagen synthesis when co-cultured specifically with type E ECs, highlighting an indispensable role in endochondral ossification during long bone formation. Mechanistic intercellular crosstalk analyses demonstrated that BMP signaling plays an essential role in modulating type E endothelial cell-mediated regulation of SSPC potency through the coordinated actions of transcription factors ID1, MSX2, and SOX9. Notably, pharmacological inhibition of BMP signaling abolished the pro-chondrogenic and pro-osteogenic enhancement conferred by type E ECs upon SSPCs.</div></div><div><h3>Conclusion</h3><div>These findings uncover a fundamental mechanism of long bone development mediated by CD140a ⁺ PDPN ⁺ SSPCs and modulated by type E ECs. This reciprocal, bipotent coupling between skeletogenesis and angiogenesis provides a conceptual framework for understanding skeletal development and homeostasis, proffering novel therapeutic avenues for associated pathologies.</div></div><div><h3>The translational potential of this article</h3><div>By elucidating the regulatory function of type E endothelial cells in orchestrating chondrogenic priming during embryonic skeletogenesis, this study unveils potential therapeutic strategies for bone regeneration through targeting the vascular network.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"58 ","pages":"Article 101123"},"PeriodicalIF":5.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147951590","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":"Deciphering inter-organ communication: The multi-organ-bone axis in osteoporosis and emerging therapeutic strategies","authors":"Ruiming Wen ,&nbsp;Haixia Wang ,&nbsp;Songtao Wang","doi":"10.1016/j.jot.2026.101119","DOIUrl":"10.1016/j.jot.2026.101119","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;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.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;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.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;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.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;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.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;The translational potential of this article is as follows&lt;/h3&gt;&lt;div&gt;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":"Advances of piezoelectric biomaterials in bone defect repair: The role of direct and inverse piezoelectric effect","authors":"Yuqi Dong ,&nbsp;Sijia Zhang ,&nbsp;Tingyu Xu ,&nbsp;Wei Sun ,&nbsp;Xiaohan Liu","doi":"10.1016/j.jot.2026.101106","DOIUrl":"10.1016/j.jot.2026.101106","url":null,"abstract":"<div><div>Natural bone exhibits piezoelectric properties due to its collagen structure. Piezoelectric biomaterials, which can replicate the electromechanical behavior of bone, have thus become a key focus in the development of artificial biomaterials. Their piezoelectricity is expressed as the direct effect under mechanical stimulation and the inverse effect under electrical stimulation. Studies have shown that appropriate mechanical or electrical cues can enhance bone defect repair by activating the piezoelectric properties of these materials, influencing osteogenesis, angiogenesis, osteoclastogenesis, inflammatory responses, and neurogenesis. This review summarizes the mechanisms through which piezoelectric biomaterials facilitate bone defect repair via direct and inverse piezoelectric effects, and discusses the current challenges and future prospects for their application in accelerating bone healing.</div><div>The Translational Potential of this Article.</div><div>This review provides a comprehensive overview of the mechanisms by which direct and inverse piezoelectric effects in piezoelectric biomaterials facilitate bone defect repair. It highlights their roles in promoting osteogenesis, angiogenesis, and neurogenesis, inhibiting osteoclast differentiation, and modulating inflammatory responses. These insights are critical for the development of novel piezoelectric biomaterials and the advancement of their personalized clinical applications.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"58 ","pages":"Article 101106"},"PeriodicalIF":5.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147858615","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":"Toward next-generation hip implants: From failure mechanisms to translational design","authors":"Yunhua Luo ,&nbsp;Thomas Turgeon ,&nbsp;Ian Polyzois","doi":"10.1016/j.jot.2026.101122","DOIUrl":"10.1016/j.jot.2026.101122","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Total hip replacement (THR) is highly successful in restoring mobility after hip fracture, yet long-term complications such as aseptic loosening, periprosthetic fracture, wear-induced osteolysis, and stress shielding continue to limit implant longevity. These failure modes largely originate from the inability of monolithic implant designs to satisfy the heterogeneous mechanical and biological requirements of the proximal femur. Their uniform material properties and fixed architecture hinder physiological load transfer, compromise osseointegration, and accelerate bone loss. Functionally graded hip scaffold–implant hybrids (FG-HSIHs) have emerged as a promising next-generation solution, offering spatial control over stiffness, porosity, degradation behavior, and surface bioactivity within a single construct to better mimic the structure and function of healthy bone.&lt;/div&gt;&lt;div&gt;This review synthesizes advances in clinical understanding, biomechanics, mechanobiology, and computational modeling relevant to the development of FG-HSIHs. We first examine the biological pathways and biomechanical mechanisms underlying major THR complications, highlighting the inherent conflicts among desired material and structural properties. These mechanistic insights form the basis for simulation-guided strategies that enable spatially adaptive design tailored to mitigate specific failure risks. We then evaluate current progress in mechanical modeling, mechanobiological simulation, multiphysics analysis, and multi-objective optimization, and assess how these components contribute to an integrated design workflow. Despite rapid progress, no existing framework fully unifies mechanical, biological, transport, and degradation processes or incorporates patient-specific biological factors. Key challenges remain in defining physiologically grounded grading targets, establishing predictive validation pipelines, and implementing multiphysics-driven design tools suitable for translational use. Overall, the purpose of this review is to assemble a coherent, field-wide perspective on the clinical, biomechanical, biological, and computational considerations relevant to FG-HSIH design, rather than cataloging all technical details.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Translational potential of this article&lt;/h3&gt;&lt;div&gt;The framework presented in this review provides a structured pathway for translating functionally graded hip scaffold–implant hybrids from concept to clinically testable prototypes. By linking THR failure mechanisms with biomechanical requirements, biological pathways, and computational design strategies, the review identifies actionable targets for implant innovation and preclinical development. The synthesis of mechanical modeling, mechanobiology, and multiphysics optimization offers a roadmap for generating designs that more effectively integrate with host bone and reduce long-term revision risk. The identified translational gaps—including the lack of integrated mechanobiologic","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"58 ","pages":"Article 101122"},"PeriodicalIF":5.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147996315","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":"Osteocytic Pink1/Prkn modulates M6P metabolism and contributes to GC-induced bone loss","authors":"Jialun Mei ,&nbsp;Zhikai Zheng ,&nbsp;Delin Liu ,&nbsp;Jian Zhou ,&nbsp;Chuan Gao ,&nbsp;Yiyang Ma ,&nbsp;Peng Ding ,&nbsp;Junjie Gao ,&nbsp;Yigang Huang ,&nbsp;Jimin Yin","doi":"10.1016/j.jot.2026.101103","DOIUrl":"10.1016/j.jot.2026.101103","url":null,"abstract":"<div><h3>Background</h3><div>Glucocorticoid-induced osteoporosis (GIOP) is largely driven by osteocyte dysfunction, which disrupts the balance between bone formation and bone resorption. The <em>Pink1/Prkn</em>-mediated mitophagy pathway plays a crucial role in maintaining mitochondrial and metabolic homeostasis in osteocytes; however, its involvement in GIOP remains unclear.</div></div><div><h3>Methods</h3><div>Osteocyte-specific <em>Pink1</em> and <em>Prkn</em> conditional knockout mice (<em>Dmp1</em>^<em>cre</em><em>Pink1</em> ^{<em>fl/fl</em>} and <em>Dmp1</em>^<em>cre</em><em>Prkn</em> ^{<em>fl/fl</em>}) were generated to investigate the role of osteocytic <em>Pink1/Prkn</em> in bone homeostasis under glucocorticoid (GC) exposure. Micro-computed tomography, histological analyses, transcriptomic and metabolomic profiling, and osteocyte–osteoblast/osteoclast co-culture assays were performed to evaluate skeletal phenotypes and metabolic alterations.</div></div><div><h3>Results</h3><div>Deletion of <em>Pink1</em> or <em>Prkn</em> in osteocytes did not affect bone mass under basal conditions but significantly aggravated GC-induced bone loss. Osteocytic Pink1/Prkn deficiency was associated with enhanced osteoclast activation and impaired osteoblast function. Integrated transcriptomic and metabolomic analyses indicated marked alterations in glycolytic and mannose-related metabolism, including a consistent reduction in mannose-6-phosphate (M6P) accompanied by reduced expression of its key biosynthetic enzyme, phosphomannose isomerase (MPI). Functionally, supplementation with exogenous M6P restored the osteoclast–osteoblast balance in <em>Pink1/Prkn</em>-deficient osteocytes in vitro. In vivo, D-mannose supplementation alleviated GC-induced bone loss in both osteocytic <em>Pink1/Prkn</em> knockout and wild-type mice.</div></div><div><h3>Conclusion</h3><div>These findings identify a previously unrecognized potential <em>Pink1/Prkn</em>–MPI–M6P metabolic axis that can contribute to osteocyte function under GC stress and highlight mannose/M6P metabolism as a potential therapeutic target for glucocorticoid-induced osteoporosis.</div></div><div><h3>The Translational Potential of This Article</h3><div>This study identifies a previously unrecognized <em>Pink1/Prkn</em>–MPI–M6P metabolic axis in osteocytes that protects against glucocorticoid-induced bone loss. By linking mitochondrial quality control to mannose metabolism and osteocyte-mediated regulation of bone remodeling, our findings provide mechanistic insight into the pathogenesis of glucocorticoid-induced osteoporosis. Importantly, the observation that D-mannose supplementation alleviates bone loss suggests that targeting mannose/M6P metabolism may represent a novel therapeutic strategy for preventing or treating GIOP.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"58 ","pages":"Article 101103"},"PeriodicalIF":5.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147951598","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}