Journal of Orthopaedic Translation最新文献

{"title":"Advancing the continuum of orthopaedic translation: Mechanistic insight, regenerative innovation, and converging technologies","authors":"Martin J. Stoddart, Geoff Richards","doi":"10.1016/j.jot.2026.101068","DOIUrl":"10.1016/j.jot.2026.101068","url":null,"abstract":"","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"56 ","pages":"Article 101068"},"PeriodicalIF":5.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147420857","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":"Spatially resolved single-cell-based histocytomorphometry for growth plate analysis across multiple species","authors":"Hantang Wang , Lanlan Zhang , Yuqi Zhang , Wei Wang , Junguo Ni , Jun Liu , Weiyuan Gong , Man Ting Au , Martin Ho Yin Yeung , Huiling Cao , Chunyi Wen","doi":"10.1016/j.jot.2025.10.007","DOIUrl":"10.1016/j.jot.2025.10.007","url":null,"abstract":"<div><h3>Background</h3><div>Current methods to assess growth plate predominantly rely on rudimentary metrics such as tissue thickness, which fail to capture the dynamic, spatial and functional heterogeneity of chondrocyte populations during endochondral ossification. To address this gap, we developed a computational histomorphometric pipeline (Growth Plate Professional Analyzer, “GP Pro”), designed to quantify chondrocyte kinetics and maturation gradients at single-cell resolution using routine histological tissue sections.</div></div><div><h3>Methods</h3><div>GP Pro integrates three automated modules: (1) batch processing of whole-slide images (WSIs) with growth plate localization, (2) segmentation of the growth plate using Segment Anything Model 2 (SAM2), and (3) single-cell lacunae analysis to extract morphometric and spatial distribution features across differentiation stages. For GP PRO's feasibility study, we conducted high-throughput testing on mouse/hamster/rat knee sections stained with Safranin-O/fastgreen (Safranin-O) and Hematoxylin & Eosin (H&E) to evaluate the computational efficiency and accuracy of the whole system and built-in functions. For GP PRO's application validation, tibial growth plates from normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHRs) were tested by the pipeline, correlating outputs with histochemical staining and micro-CT scanning results.</div></div><div><h3>Results</h3><div>GP PRO demonstrates satisfactory computational efficiency, with a processing time as low as 3.6 s per section and achieves an end-to-end automated processing success rate of above 95 %. Additionally, it boasts an average chondrocyte identification accuracy of 90.28 % and a macro-precision of 94.76 % in cell classification. In the application of SHR, GP Pro revealed a 4.03 percentage points increase in proliferative chondrocyte proportion (p < 0.05; 95 % CI: 0.59–7.47) and the presence of aberrantly elongated pre-hypertrophic chondrocytes at 3-month-old, indicative of maturation arrest. These cellular perturbations aligned with micro-CT showing a 36.04 percentage points decrease in primary spongiosa bone volume fraction (p < 0.001; 95 % CI: 30.10–41.97), suggesting compromised osteogenic coupling. Histology confirmed premature hyperproliferation and delayed hypertrophic differentiation in SHR growth plates.</div></div><div><h3>Conclusion</h3><div>GP Pro establishes a scalable platform for mapping chondrocyte behavior in situ, enabling unprecedented resolution of growth plate pathobiology. By linking hypertrophic differentiation delays to trabecular bone deficits in hypertension, this tool advances mechanistic studies of endochondral ossification and offers translational potential for diagnosing growth disorders or monitoring therapeutic interventions in multiple species.</div></div><div><h3>The Translational Potential of this Article</h3><div>This study introduces GP Pro, an AI-driven histomorphometric pl","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"56 ","pages":"Article 101015"},"PeriodicalIF":5.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147420116","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":"Systemic inflammatory perturbations triggered by neuropathic pain in L5 compressed mouse and rat model","authors":"Shangmin Chen ,&nbsp;Zhikai Zheng ,&nbsp;Hua Ying ,&nbsp;Fang Ye ,&nbsp;Peng Liao ,&nbsp;Jian Zhou ,&nbsp;Sihan Tong ,&nbsp;Junjie Gao ,&nbsp;Delin Liu ,&nbsp;Zhigang Zhong ,&nbsp;Yi-Gang Huang","doi":"10.1016/j.jot.2025.10.006","DOIUrl":"10.1016/j.jot.2025.10.006","url":null,"abstract":"<div><h3>Background</h3><div>Neuropathic pain is caused by lesions or disease affecting the somatosensory nervous system either in the periphery or centrally. Unresolvable inflammation is one of the main causes of the difficulty in managing prolonged pain. Although neuropathic pain is characterized by local inflammatory infiltration at the lesion site, whether neuropathic pain can induce systemic inflammation and the underlying mechanisms remain unknown.</div></div><div><h3>Methods</h3><div>The systematically effects of neuropathic pain was we investigated by using lumbar 5 (L5) nerve compression mouse and rat model and performed multi-omic analysis on multiple organ systems at three levels: (1) local compressed nerves (L4-6), (2) brain and bone marrow, and (3) major indirect organs (including heart, liver, lung, kidney, colon, small intestine, spine and spleen).</div></div><div><h3>Results</h3><div>Bulk RNA sequencing of nerves (L4-6) revealed L5 compression resulted in inflammatory response, metabolic disorders, neuron regeneration. Single-cell RNA sequencing of bone marrow and brain cells identified perturbations in neutrophils and macrophages within the bone marrow, and in microglia within the brain, highlighting the upregulation of inflammatory and immune response pathways. Further ATAC sequencing of bone marrow-derived macrophages revealed upregulation of Rho protein signal transduction and small GTPase-mediated signal transduction. Bulk RNA sequencing of major organs (heart, liver, lung, kidney, colon, small intestine, spine and spleen) revealed activated immune and dysregulated lipid metabolism, with macrophages playing a key role in the process through the activation of different pathways.</div></div><div><h3>Conclusion</h3><div>Our study reveals that nerve compression-induced neuropathic pain triggers systemic inflammation, characterized by upregulated expression of pro-inflammatory genes (IL13 and Csf3 in bone marrow and brain; TNF-α in the compressed nerve), altered chromatin accessibility in bone marrow macrophages, increased aerobic respiration and energy metabolism in the lungs, hepatic metabolic dysfunction, and renal lipid accumulation. Additionally, ligand-receptor networks facilitate cross-organ inflammation. This atlas redefines neuropathic pain as a multi-organ disorder and identifies myeloid-immune signaling pathways as potential therapeutic targets.</div></div><div><h3>The translational potential of this article</h3><div>Our study identifies key genes and signaling pathways that may contribute to systemic inflammation in nerve compression-induced neuropathic pain. We sorted out potential intervention targets to modulate the inflammatory process in neuropathic pain, such as inhibitors of Csf3 and IL13, as well as targeting the IL6/TNF-α pathway. However, further functional validation is necessary to confirm their therapeutic efficacy.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"56 ","pages":"Article 101014"},"PeriodicalIF":5.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147420115","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":"Immunoregulatory orchestrations in osteoarthritis and mesenchymal stromal cells for therapy","authors":"Tongmeng Jiang ,&nbsp;Shibo Su ,&nbsp;Ruijiao Tian ,&nbsp;Yang Jiao ,&nbsp;Shudan Zheng ,&nbsp;Tianyi Liu ,&nbsp;Yang Yu ,&nbsp;Pengbing Hua ,&nbsp;Xiuhong Cao ,&nbsp;Yanlong Xing ,&nbsp;Panli Ni ,&nbsp;Rui Wang ,&nbsp;Fabiao Yu ,&nbsp;Juan Wang","doi":"10.1016/j.jot.2025.08.009","DOIUrl":"10.1016/j.jot.2025.08.009","url":null,"abstract":"<div><div>Osteoarthritis (OA) is characterized by the inability of stable and complex joint structures to function as they did, accompanied by inflammation, tissue changes, chronic pain, and neuropathic inflammation. In the past, the primary focus on the causes of joint dysfunction has been on mechanical stress leading to cartilage wear. Further researches emphasize the aging of cartilage and subchondral bone triggered cartilage lesion and osteophyte formation. Recently, the effects of immune cells, particularly macrophages and T cells, have been receiving focused attention. Herein, we primarily discuss the role of macrophages and T cells in the progression of OA and how mild inflammation in cartilage, subchondral bone, synovium, muscles, and nerves influences the progression of OA. Additionally, this review highlights the interaction between mesenchymal stromal cells (MSCs) and macrophages, as well as MSCs and T cells, along with how these interactions affect OA development and treatment. Finally, we explore future research directions and issues that still need to be addressed, providing more insights for the clinical translation of MSC-based therapy for OA.</div></div><div><h3>The translational potential of this article</h3><div>This review highlights the promising translational potential of MSCs in OA therapy by targeting immunoregulatory networks. MSCs directly modulating macrophage M1/M2 polarization, Th1/Th2 and Th/Treg balance of T cells to suppress inflammation, thereby promoting cartilage repair and subchondral bone remodeling. Their ability to synergize with biomaterials or drug carriers enhances therapeutic precision and efficacy. However, challenges like MSCs survival in inflammatory microenvironments, heterogeneity in immune cell responses, and personalized treatment strategies require further optimization. Advances in genetical engineered strategies, extracellular vesicles, scaffolds/hydrogels or nanoparticle-based approaches may bridge these gaps, offering scalable solutions for clinical translation. This work underscores MSC-based therapies as a transformative approach for OA, pending refinement of delivery systems and patient stratification.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"55 ","pages":"Pages 38-54"},"PeriodicalIF":5.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144904569","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":"Preclinical validation of finite element models for predicting in vivo residual plate bending using continuous implant sensor data","authors":"Dominic Mischler ,&nbsp;Manuela Ernst ,&nbsp;Peter Varga","doi":"10.1016/j.jot.2025.08.001","DOIUrl":"10.1016/j.jot.2025.08.001","url":null,"abstract":"<div><h3>Background/objective</h3><div>Plate failure, including bending, is a critical issue in orthopedic fracture fixation, with clinical failure rates of 3.5%–19%, burdening patients and healthcare systems. Preclinical ovine models have observed similar plate bending due to overloading. Finite element (FE) models could be capable of predicting failures but lack <em>in vivo</em> loading data for validation. The AO Fracture Monitor is an implantable sensor that can continuously track implant deformation, offering a proxy for implant loading and the potential to bridge this gap. This study aimed to preclinically validate an FE simulation methodology for predicting overloading bending of locking plates in an ovine tibia osteotomy model using AO Fracture Monitor data, emphasizing its potential for clinical translation.</div></div><div><h3>Methods</h3><div>Tibiae of eleven sheep with osteotomy gaps (0.6 – 30 mm) were instrumented with stainless steel or titanium locking plates equipped with AO Fracture Monitors in a prior study. Residual plate bending angles were measured using co-registered CT scans at 0 and 4 weeks post-operation, with bending defined as ≥ 1°. Animal-specific FE models, incorporating virtual AO Fracture Monitors and non-linear implant material properties, were developed to determine sensor signals at the construct's yield point. <em>In vivo</em> sensor signals were compared to the virtual plasticity threshold to predict CT-based residual bending outcomes.</div></div><div><h3>Results</h3><div>Within 4 weeks, plate bending angles ranged from 0.4° to 10.4°, with overloading bending observed in 6 animals. The FE methodology correctly predicted bending/no-bending outcomes in 9 of 11 animals, achieving 100% sensitivity and 60% specificity.</div></div><div><h3>Conclusions</h3><div>This sensor-validated FE methodology robustly predicted <em>in vivo</em> plate bending, offering a promising tool for reducing implant failure. These findings highlight the methodology's ability to detect clinically relevant bending outcomes. By integrating real-time loading data, it supports the development of personalized rehabilitation strategies, enhancing clinical outcomes in fracture fixation.</div></div><div><h3>The Translational Potential of this Article</h3><div>This validated FE methodology, leveraging AO Fracture Monitor data, can be adapted for human use to tailor rehabilitation protocols immediately post-surgery and provide real-time feedback to patients and clinicians if loading exceeds safe thresholds. This approach could minimize implant failure, reduce revision surgeries, and enhance patient recovery.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"55 ","pages":"Pages 55-61"},"PeriodicalIF":5.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144906944","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":"Single-cell RNA sequencing reveals early cell dynamics of MSC-based therapy in long bone critical-size defects in mice","authors":"Ning Zhang ,&nbsp;Jie Yuan ,&nbsp;Xueping Li ,&nbsp;Ni Su ,&nbsp;Yiyun Wang ,&nbsp;Shuxian Chen ,&nbsp;Ejun Huang ,&nbsp;Qi Gao ,&nbsp;Fan Yang ,&nbsp;Simon Kwoon-Ho Chow ,&nbsp;Stuart B. Goodman","doi":"10.1016/j.jot.2025.08.007","DOIUrl":"10.1016/j.jot.2025.08.007","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Bone defects resulting from various causes present significant challenges in obtaining robust bone healing. This clinical scenario is particularly difficult in cases involving large bone defects, often leading to delayed union or non-union. Autogenous bone graft is the gold standard, but it is limited by the quantity and quality of available bone. Mesenchymal stem cells (MSCs) have shown promise in enhancing bone defect healing; however, the mechanisms by which MSCs modify the local bone microenvironment and interact with other cells early in the healing process are not fully understood. Elucidating and modulating the early biological events relevant to the healing of bone defects could lead to novel therapies to obtain a more expeditious and complete outcome.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Critical-size femoral defects were created in 10 to 12-week-old BALB/c male mice and fixed with an external fixation device. Four weeks after the generation of the defect, secondary surgeries were performed. Mice were randomized into three groups based on the secondary surgery: Empty group - surgery was performed without implanting scaffolds or cells. Sc group - a 2 mm diameter cylindrical microribbon (μRB) scaffold was implanted into the defect site. Sc + MSC group - a scaffold embedded with MSCs was implanted into the bone defect site. One week after the secondary surgeries, the entire tissue within the bone defect site was harvested for single-cell RNA sequencing (scRNA-seq).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Uniform manifold approximation and projection (UMAP) plots with quality filtered cells from three groups were used to identify the cell distributions in the defects. We identified thirteen populations and annotated each cluster using UMAP with Louvain clustering on combined single cells of three groups based on marker gene expression. Different cell compositions were revealed, especially the proportion of various types of immune cells in the Sc vs Sc + MSC groups. MSCs and osteoblastic lineage cells (MSC/Osteo), and osteoclasts were almost exclusively found in the Sc + MSC group. Differential gene expression and pathway analysis in major cell populations identified immune cell changes and inflammatory changes in the presence of implanted MSCs. Cell–cell communications revealed a greater number of interactions between different cell types in the Sc and Sc + MSC groups. More interactions among MSCs, macrophages, and T cells were observed in Sc + MSC groups. MSC demonstrated the highest outgoing interaction strength in all groups.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;In the critical-size bone defect model, a combination of MSCs with μRB scaffolds showed an increased presence of mesenchymal lineage cells and promoted the further recruitment of macrophages and osteoclasts at 1 week. This alteration in the local immune landscape and microenvironment could enhance the cellular dynamics of critical cell populations tha","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"55 ","pages":"Pages 121-131"},"PeriodicalIF":5.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145019904","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":"Epigenetic reprogramming via EZH2 inhibition rescues fibroadipose pathogenesis in secondary lymphedema through activating PPARγ signaling","authors":"Ziyu Chen ,&nbsp;Zhi Yao ,&nbsp;Mengfan Wu ,&nbsp;Yuluan Wu ,&nbsp;Jianlin Zhang ,&nbsp;Zhuangyao Liao ,&nbsp;Junyu Qian ,&nbsp;Jiewen Wei ,&nbsp;Lili Song ,&nbsp;Longbiao Yu ,&nbsp;Jingjing Wen ,&nbsp;Zhegang Zhou ,&nbsp;Yihao Wei ,&nbsp;Yuefeng Yao ,&nbsp;Zetao Ma ,&nbsp;Pei Liu ,&nbsp;Shailesh Agarwal ,&nbsp;Ye Li ,&nbsp;Lixiang Xue ,&nbsp;Deli Wang","doi":"10.1016/j.jot.2025.08.014","DOIUrl":"10.1016/j.jot.2025.08.014","url":null,"abstract":"<div><h3>Background</h3><div>Secondary lymphedema, a progressive disorder characterized by pathological fibroadipose tissue accumulation, is a common problem after cancer treatment and orthopedic surgery. It remains a therapeutic enigma due to its self-perpetuating fibrotic cascade and lack of disease-modifying therapies. While current therapeutic approaches focus on symptom management and volume reduction, they don't address the epigenetic reprogramming driving fibrotic commitment—a process recently linked to enhancer of zeste homolog 2 (EZH2). Although EZH2 inhibitor EPZ6438 has been approved for clinical application, its therapeutic potential in fibroadipose pathogenesis remains unexplored, leaving a critical gap in understanding epigenetic factors in lymphedema progression.</div></div><div><h3>Methods</h3><div>Human skin tissue was collected from lymphedema patients and normal controls. Histological/immunofluorescence staining and RNA sequencing were performed. In vivo, a mouse hind limb secondary lymphedema model was established by lymphadenectomy. EZH2 inhibitors (EPZ6438, GSK126) were intraperitoneally injected. Skin samples were collected for histological assessment and immuno-staining. In vitro, adipose-derived mesenchymal stem cells (AdMSCs) were treated with transforming growth factor beta 1 (TGFβ1) and EZH2 inhibitors. Western blot, RT-qPCR and ChIP-qPCR were carried out.</div></div><div><h3>Results</h3><div>Fibrous tissue was observed in lymphedema samples, with concomitant elevation of EZH2 and H3K27me3 levels in the nucleus. RNA sequencing and gene set enrichment analysis (GSEA) revealed significant downregulation of the peroxisome proliferator-activated receptor (PPAR) signaling in lymphedema tissue. Pharmacological inhibition of EZH2 significantly attenuated cutaneous thickening, fibroadipose layer expansion, and collagen deposition in the mouse lymphedema model. PPARγ was induced while phospho-SMAD2/3 activation was suppressed. In TGFβ1 stimulated AdMSCs, EZH2 inhibition upregulated PPARγ expression and inhibited fibrogenic differentiation of the cells.</div></div><div><h3>Conclusion</h3><div>EZH2 inhibitors exerted potent anti-fibrotic effects in secondary lymphedema though activating PPARγ signaling, offering novel insights and strategies for fibrotic disorders.</div></div><div><h3>The translational potential of this article</h3><div>This study demonstrated that targeted inhibition of the EZH2-PPARγ axis effectively inhibited fibrogenic differentiation of AdMSCs and reduced fibroadipose tissue in secondary lymphedema, indicating it is a promising strategy for secondary lymphedema treatment, offering novel insights and strategy for musculoskeletal fibrotic disorders.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"55 ","pages":"Pages 309-322"},"PeriodicalIF":5.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145220802","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":"Targeting ANT1 to regulate PINK1/Parkin-mediated mitophagy is an effective treatment of trauma-induced tendon heterotopic ossification","authors":"Guanzhi Li ,&nbsp;Tong Li ,&nbsp;Ye Deng ,&nbsp;Xiao Deng ,&nbsp;Chao Chen ,&nbsp;Bin Yu ,&nbsp;Kairui Zhang","doi":"10.1016/j.jot.2025.08.002","DOIUrl":"10.1016/j.jot.2025.08.002","url":null,"abstract":"<div><h3>Background</h3><div>Heterotopic ossification (HO) is a common degenerative disease following trauma. Tendon HO is primarily attributed to osteogenic differentiation of stem/progenitor cells within the tendon. However, the precise mechanism underlying this process remains unclear. Recent studies suggest that PTEN induced kinase 1 (PINK1)/Parkin-mediated mitophagy plays a crucial role in biomineralization. Adenine nucleotide translocase 1 (ANT1), an upstream regulator of the PINK1/Parkin pathway, may influence tendon ossification development by modulating mitophagy.</div></div><div><h3>Methods</h3><div>This study investigated the role of mitophagy in tendon osteogenesis in clinical specimens, mouse tissues, and cells. The impact of ANT1 on tendon osteogenesis through mitophagy regulation was assessed by knocking down solute carrier family 25 member 4 (<em>Slc25a4)</em> both <em>in vitro</em> and <em>in vivo</em>. Furthermore, elamipretide was identified as a potential targeted drug for ANT1 through computer virtual screening and experimental verification. Its therapeutic efficacy on tendon ossification was validated using mouse cells, tissues, and human cells.</div></div><div><h3>Results</h3><div>This study found that PINK1/Parkin-mediated mitophagy was activated during tendon ossification, and the regulation of mitophagy could impact the osteogenesis of injured tendon-derived progenitor cells (inTPCs). Loss of <em>Slc25a4</em> inhibited tendon ossification by downregulating the excessive mitophagy. Elamipretide, a targeted drug for ANT1, showed significant efficacy in treating HO.</div></div><div><h3>Conclusion</h3><div>Modulating PINK1/Parkin-mediated mitophagy by targeting ANT1 mitigated the progression of trauma-induced tendon HO, indicating ANT1 can be a potential therapeutic target for HO, with elamipretide emerging as a promising drug for its treatment.</div></div><div><h3>The translational potential of this article</h3><div>This study identifies ANT1 as a therapeutic target and supports elamipretide as a promising treatment strategy for HO.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"55 ","pages":"Pages 1-21"},"PeriodicalIF":5.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144894810","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":"Development and multi-center validation of a software program, Ofeye 3.0, for automated all-inclusive vertebral fracture detection with chest/abdominal CT images","authors":"Ben-Heng Xiao ,&nbsp;Zhen-Hua Gao ,&nbsp;Cai-Ying Li ,&nbsp;Xiao-Ming Leng ,&nbsp;Er-Zhu Du ,&nbsp;Jian-Bing Ma ,&nbsp;Fu-Shan Liu ,&nbsp;Jing-Shan Gong ,&nbsp;Zhi-Guo Ju ,&nbsp;Ming-Yuan Yuan ,&nbsp;Hui-Ming Zhu ,&nbsp;Michael S.Y. Zhu ,&nbsp;Timothy YC. Kwok ,&nbsp;Yì Xiáng J. Wáng","doi":"10.1016/j.jot.2025.08.011","DOIUrl":"10.1016/j.jot.2025.08.011","url":null,"abstract":"<div><h3>Background</h3><div>Missing report for fragility vertebral fracture (VF) on chest/abdominal CT is common when the indication is not spine disorders. This represents a missed opportunity to alert patients to take preventive measures to improve bone health and prevent further severe fractures. In this study, we aim to develop a software program for automated detection of VF with existing chest/abdominal CT scans and validate its detection performance.</div></div><div><h3>Methods</h3><div>An automated sagittal Central Slab reconstruction (CSR) method for CT axial images was developed. For reference VF reading<em>,</em> VFs inclusive of those of with &lt;20 % vertebral height loss and those of endplate fracture with minimal vertebral height loss were identified. VFs were also differentiated from osteoarthritic wedging and endplatitis short vertebrae. Prior knowledge of VF detection models for lateral radiograph were transferred to a new ‘Ofeye 3.0’ model optimized for VF detection on CT image. Training CT images were obtained from nine centers, totaling 3313 cases without VF and 835 cases with VF. For external validation, CT images were from five centers totaling 732 cases without VF and 224 cases with VF.</div></div><div><h3>Results</h3><div>The automated CSR method showed advantages in demonstrating structural changes of the endplate and adjacent structures. For detecting VF in chest/abdominal CT scans, counting case-by-case and compared with the reference reading, the average performance of Ofeye 3.0 was accuracy 0.967, sensitivity 0.906, and specificity 0.986. Most of false negative or false positive cases were minimal or mild VF, or with image artifacts, or with VF close to the peripheral of CSR images.</div></div><div><h3>Conclusions</h3><div>Despite the challenging requirements for the software to detect all-inclusive VF, our results compare favorably with other published automated VF detection models.</div></div><div><h3>The translational potential of this article</h3><div>We developed a software program for automated all-inclusive VF detection on chest and/or abdominal CT image data and conducted a multi-center external validation study. This software is proved to have high VF detection precision. By alerting patients of the VFs likely related to osteoporosis and in turn the patients taking measures to prevent further fracture, the integration of this software into radiological practice will improve patient outcomes and reduce healthcare costs.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"55 ","pages":"Pages 192-203"},"PeriodicalIF":5.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145045683","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":"Advanced bioactive materials and strategies for tendon repair and function restoration","authors":"Sidan Wang ,&nbsp;Zixuan Ou ,&nbsp;Feng Xiao ,&nbsp;Xiaobo Feng ,&nbsp;Lei Tan ,&nbsp;Shuangshuang Cheng ,&nbsp;Di Wu ,&nbsp;Cao Yang ,&nbsp;Haoqun Yao","doi":"10.1016/j.jot.2025.08.012","DOIUrl":"10.1016/j.jot.2025.08.012","url":null,"abstract":"<div><div>Tendon injury is one of the most common clinical challenges in musculoskeletal disorders. Effective tendon repair is crucial for restoring patients' motor function and improving their quality of life. Recent advances in bioactive material-mediated tendon regeneration have shown great therapeutic potential and clinical relevance. However, systematic reviews that comprehensively integrate these developments are still scarce. Firstly, this article presents the selection of bioactive components, mainly including cell-based therapeutic strategies and nanodrug delivery strategies. Secondly, bioactive materials delivery system using tissue-engineered scaffolds is discussed in detail. In this section, we discuss the efficacy of scaffolds in tendon repair through different scaffold preparation methods and synthetic raw materials. Furthermore, the application of hydrogel systems such as enhanced hydrogels, bioadhesive hydrogels and multifunctional hydrogels in tendon repair strategies is systematically and comprehensively presented. Finally, based on a detailed review of the field, current challenges in the field were proposed and potential research directions in the field were identified, including potential research directions in smart bioactive materials and personalized treatment strategies.</div></div><div><h3>The translational potential of this article</h3><div>This review synthesizes tendon regeneration strategies—from molecular mechanisms to tissue-level integration—including bioactive component selection and delivery systems using tissue-engineered scaffolds. It identifies translational barriers and proposes new strategies in tendon-specific safety validation, scalable manufacturing uniformity and cost-effectiveness versus conventional therapies. These insights will refine clinical strategies for tendon injuries and advance targeted bioactive biomaterials for localized regeneration.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"55 ","pages":"Pages 204-227"},"PeriodicalIF":5.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145060059","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}