Journal of Orthopaedic Translation最新文献

{"title":"Corrigendum to “Bioabsorbable magnesium-based bulk metallic glass composite (BMGC) for improved medial opening wedge high tibial osteotomy in knee osteoarthritis” [J Orthop Transl 50, January 2025, Pages 97-110]","authors":"Kuan-Hao Chen , Pei-Chun Wong , Lekha Rethi , Wei-Ru Wang , Chieh-Ying Chen , Pei-Hua Tsai , Jason Shian-Ching Jang , Chun-Li Lin , Chih-Hwa Chen , Andrew E.-Y. Chuang","doi":"10.1016/j.jot.2025.11.006","DOIUrl":"10.1016/j.jot.2025.11.006","url":null,"abstract":"","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"57 ","pages":"Article 101030"},"PeriodicalIF":5.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147348520","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":"TRIM59 alleviates neuronal ferroptosis and promotes functional recovery after spinal cord injury by mediating ubiquitination and degradation of ANXA2","authors":"Tao Hu ,&nbsp;Wei Wang ,&nbsp;Xuan Zhao ,&nbsp;Peng Cui ,&nbsp;Haojie Zhang ,&nbsp;Zuoran Fan ,&nbsp;Dongfan Wang ,&nbsp;Xinli Hu ,&nbsp;Haixia Huang ,&nbsp;Xiaolong Chen ,&nbsp;Yuluo Rong ,&nbsp;Shibao Lu","doi":"10.1016/j.jot.2026.101070","DOIUrl":"10.1016/j.jot.2026.101070","url":null,"abstract":"<div><h3>Background</h3><div>Spinal cord injury (SCI) is a severe central nervous system disorder for which effective therapeutic interventions remain limited. Accumulating evidence indicates that ferroptosis is a key contributor to secondary neuronal damage following SCI, yet its upstream regulators—particularly those involving post-translational modifications such as ubiquitination—remain incompletely understood. This study aimed to determine whether the E3 ubiquitin ligase TRIM59 modulates neuronal ferroptosis and functional recovery after SCI, and to elucidate its molecular substrate and underlying mechanism of action.</div></div><div><h3>Methods</h3><div>TRIM59 expression was modulated using lentiviral vectors in cultured neurons and adeno-associated virus serotype 9 (AAV9) in mice. Functional recovery was assessed through the BMS, inclined plane test, footprint analysis, and motor evoked potentials. Ferroptosis was evaluated via biochemical assays, BODIPY C11 staining, ROS detection, TEM, and ferroptosis markers. Molecular interactions were analyzed by co-immunoprecipitation (Co-IP), ubiquitination assays, and cycloheximide (CHX) chase experiment.</div></div><div><h3>Results</h3><div>TRIM59 expression was significantly downregulated during Erastin-induced ferroptosis in neurons and in spinal cord tissue during the acute phase (days 1–3) after SCI. Downregulation of TRIM59 exacerbated the hallmark features of ferroptosis and impaired motor recovery, whereas TRIM59 overexpression attenuated ferroptosis and promoted neurological restoration. Mechanistically, TRIM59 directly bound to ANXA2 and mediated its K48-linked polyubiquitination and subsequent proteasomal degradation. The neuroprotective effect of TRIM59 was abolished by a catalytically inactive C30A mutant or by ANXA2 overexpression, whereas ANXA2 knockdown rescued the ferroptosis and functional deficits induced by TRIM59 deficiency.</div></div><div><h3>Conclusion</h3><div>This study identifies a novel TRIM59–ANXA2 regulatory axis that critically governs neuronal ferroptosis and functional recovery after SCI. TRIM59 functions as an endogenous suppressor of ferroptosis by targeting ANXA2 for K48-linked ubiquitin–proteasome–mediated degradation. These findings not only elucidate a key post-translational mechanism in SCI pathophysiology but also position TRIM59 as a promising therapeutic target for neuroprotection and functional restoration following SCI.</div></div><div><h3>The translational potential of this article</h3><div>Targeting the TRIM59–ANXA2 pathway offers a promising therapeutic strategy to inhibit ferroptosis and promote neuroprotection and functional recovery after SCI. Enhancing TRIM59 activity or disrupting ANXA2 stability could pave the way for novel treatments in clinical neurotrauma.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"57 ","pages":"Article 101070"},"PeriodicalIF":5.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147600340","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":"Mitochondrial metabolism restoration via Tramiprosate suppresses mitochondrial ROS-driven foamy macrophage senescence post spinal cord injury","authors":"Chaoqin Wu ,&nbsp;Qihao Fu ,&nbsp;Jianlan Liu ,&nbsp;Jiajyu Fu ,&nbsp;Buzheng Zhang ,&nbsp;Jin Zhou ,&nbsp;Jiawen Xu ,&nbsp;Ying Zhang ,&nbsp;Tianyu Zhu ,&nbsp;Lei Yang ,&nbsp;Xiaojian Cao ,&nbsp;Zhanyang Qian","doi":"10.1016/j.jot.2026.101049","DOIUrl":"10.1016/j.jot.2026.101049","url":null,"abstract":"<div><h3>Background</h3><div>Myelin debris (MD) engulfment-induced foamy macrophage formation is a core neuropathology following spinal cord injury (SCI). The accumulation of these foamy macrophages within the injured foci sustains neuroinflammation, impeding long-term neuroregeneration and functional recovery. However, the mechanism underlying macrophage deterioration post-foaming remains elusive.</div></div><div><h3>Methods</h3><div>MD-induced foamy macrophage and SCI model were used to investigated the role of Tramiprosate (TMP) <em>in vivo</em> and <em>in vitro</em>. Histological staining and functional assessments (gait analysis, Basso Mouse Scale, and motor evoked potentials) were conducted to evaluate the therapeutic effects of TMP on SCI. Quantitative PCR, western blotting, flow cytometry, immunofluorescence, seahorse assay and transmission electron microscopy were used to investigate the senescence and mitochondria function in foamy macrophages. RNA sequencing revealed TMP's role in restoring mitochondrial metabolism. And we injected AAV-shRNA to examine the potential molecular mechanism of TMP.</div></div><div><h3>Results</h3><div>The current study reveals that lipid droplet-laden foamy macrophages exhibit mitochondrial dysfunction and a senescent phenotype, characterized by increased secretion of matrix metalloproteinases and proinflammatory cytokines. Restoring mitochondrial metabolism via TMP—via upregulation of Shmt2—inhibits mitochondrial reactive oxygen species (mtROS) and mitochondrial DNA (mtDNA) leakage. This reduces oxidative damage to nuclear DNA and suppresses the cyclic GMP-AMP synthase (cGAS)-mediated inflammatory response, thereby eliminating senescence in foamy macrophages.</div></div><div><h3>Conclusions</h3><div>Our work demonstrates that TMP is a potential therapeutic agent targeting mitochondrial dysfunction-induced macrophage senescence post SCI.</div></div><div><h3>The Translational Potential of this Article</h3><div>This study investigates the mechanisms underlying macrophage senescence following SCI and identifies TMP as a potential therapeutic agent to mitigate this process. Importantly, TMP is a taurine analogue with established blood–brain barrier permeability and a favorable safety profile in prior clinical investigations for neurodegenerative diseases. These characteristics support its potential treatment strategy for SCI.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"57 ","pages":"Article 101049"},"PeriodicalIF":5.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147425024","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":"Hydrogen sulfide generated by cystathionine gamma lyase inhibits lysyl oxidase and protects against calcific tendinopathy","authors":"Elodie Faure ,&nbsp;Ilaria Bernabei ,&nbsp;Driss Ehirchiou ,&nbsp;Philipp Michel ,&nbsp;Daniel Kronenberg ,&nbsp;Thomas Pap ,&nbsp;Giuseppe Cirino ,&nbsp;Richard Stange ,&nbsp;Nathalie Busso ,&nbsp;Sonia Nasi","doi":"10.1016/j.jot.2026.101082","DOIUrl":"10.1016/j.jot.2026.101082","url":null,"abstract":"<div><h3>Background/objective</h3><div>Increased lysyl oxidase (LOX) activity favors pathologic cartilage and vessel calcification. LOX promotes disease through enhanced collagen cross-linking, inflammation, reactive oxygen species (ROS) production, cell trans-differentiation, and fibrosis. This study investigates the therapeutic potential of cystathionine gamma lyase (CSE)-generated hydrogen sulfide (H₂S) to inhibit tendon calcification by targeting LOX in human samples and murine models of calcific tendinopathy (CT).</div></div><div><h3>Methods</h3><div>Human shoulder supraspinatus tendons with varying degrees of CT were analyzed using Alizarin Red staining and LOX and CSE immunohistochemistry to evaluate the correlation between CSE and LOX/calcification. Mechanistic studies were performed using wild-type (WT) and CSE knockout murine tenocytes cultured in calcification-inducing medium with or without H₂S donors or the LOX inhibitor β-aminopropionitrile (BAPN). Achilles tendon CT was induced in WT and CSE knockout mice via surgical intervention or aging. Tendon calcification, LOX expression, biomechanical integrity, and transcriptomic changes were assessed. Persulfidation of total proteins and recombinant human LOX (rhLOX) was measured using the dimedone-switch method.</div></div><div><h3>Results</h3><div>An inverse correlation between CSE levels and LOX/calcification was observed in human tendons and in the surgery-induced CT murine model. In murine tenocytes and in the aging murine model, CSE deficiency led to increased LOX expression, enhanced calcification, and reduced tendon biomechanical integrity.Transcriptomic analysis confirmed the negative association between CSE and LOX in murine CT. Mechanistically, H₂S increased total cellular protein persulfidation, including rhLOX, resulting in inhibition of its enzymatic activity.</div></div><div><h3>Conclusion</h3><div>Dysregulated LOX activity is a key driver of calcific tendinopathy. CSE-generated H₂S effectively suppresses LOX activity, highlighting its potential as a therapeutic strategy for CT and other calcification-related disorders.</div></div><div><h3>The translational potential of this article</h3><div>This study identifies LOX as a therapeutic target in CT and supports H₂S as a promising treatment strategy for this condition.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"57 ","pages":"Article 101082"},"PeriodicalIF":5.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147540218","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 in flexible wearable pressure/strain sensors for motion monitoring in orthopaedic sports medicine","authors":"Hongfu Jin ,&nbsp;Wenwu Wang ,&nbsp;Guoxu Zhang ,&nbsp;Sijie Chen ,&nbsp;Yao Tong ,&nbsp;Dan Lu ,&nbsp;Jian Li ,&nbsp;Liang He ,&nbsp;Xin Tang","doi":"10.1016/j.jot.2026.101084","DOIUrl":"10.1016/j.jot.2026.101084","url":null,"abstract":"<div><div>The growing demand for real-time, high-resolution motion monitoring in orthopaedic sports medicine is driving the development of flexible wearable pressure/strain sensors. These devices, which transduce mechanical stimuli into electrical signals via piezoresistive, capacitive, piezoelectric, electromagnetic, and triboelectric mechanisms, enable continuous biomechanical data acquisition in dynamic, real-world settings, thereby overcoming the limitations of traditional lab-based methods. This review provides a comprehensive overview of recent advances in wearable pressure/strain sensors, covering fundamental sensing mechanisms and innovative design strategies, including using elastomers, polymer thin films, electronic textiles, and hydrogels. The review also highlights key emerging trends, such as microstructured, bioinspired, multimodal, and machine-learning-enabled signal-processing designs, which have significantly enhanced sensor performance by addressing challenges such as limited sensitivity, narrow detection range, environmental interference, and long-term instability. These sensors are now integrated into wearable devices with diverse applications in orthopaedic sports medicine, including real-time motion tracking, gait analysis, injury prediction and diagnosis, rehabilitation assessment, and human-machine interaction. This review also deliberates on existing limitations and delineates future directions for translating wearable pressure/strain sensors into practical orthopaedic sports medicine applications.</div></div><div><h3>The translational potential of this article</h3><div>To address the limitations of traditional lab-bound motion monitoring, such as high costs and restricted environments, it is essential to leverage the progress in flexible wearable sensing technology. This review provides a comprehensive overview of recent advancements in wearable pressure/strain sensors, highlighting their role in capturing high-resolution biomechanical data in real-world settings. By enabling continuous motion monitoring and objective assessment, these advancements offer valuable insights to improve clinical outcomes in orthopaedic sports medicine, with significant translational potential.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"57 ","pages":"Article 101084"},"PeriodicalIF":5.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147540215","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":"Gut microbiota and bone aging: Focusing on the gut-X axis modes","authors":"Yuan-Wei Zhang ,&nbsp;Rui-Yang Li ,&nbsp;Yan Wu ,&nbsp;Peng Wang ,&nbsp;Qi-Rong Zhou ,&nbsp;Jia-Can Su","doi":"10.1016/j.jot.2026.101064","DOIUrl":"10.1016/j.jot.2026.101064","url":null,"abstract":"<div><div>As studies have continuously advanced, cross-linking interplay between various organs in aging individuals have continuously emerged as research hotspots. The role of gut microbiota in bone aging-related diseases, including osteoporosis, osteoarthritis, and intervertebral disc degeneration, has been extensively probed. This review first summarized the inseparable association between gut microbiota and osteoporosis, osteoarthritis, and intervertebral disc degeneration, which then explored potential mechanisms of gut-X axis through neuromodulation (microbiota-gut-brain-bone axis), immunomodulation (Th17 and Treg balance), endocrine regulation (gut-derived hormones and 5-HT), metabolite-mediated regulation (SCFAs), bacterial extracellular vesicles, and changes in microbial niche and gut microbiome-associated biomarkers. Moreover, potential intervention strategies including diet, probiotics, fecal microbiota transplantation, and physical activity were summarized to enhance clinical translation applicability. This review creatively exhibited integrated concept of “gut-X axis” to explore common, patterned mechanisms underlying “gut-bone axis”, “gut-joint axis”, and “gut-disc axis”. Furthermore, it delves into potential mechanisms by which this shared pattern regulates bone aging-related diseases and prospectively outlines therapeutic strategies for bone aging based on this axis.</div></div><div><h3>The translational potential of this article</h3><div>This review presents crucial role and regulatory significance of gut-X axis modes in common bone-aging related diseases. By anchoring the gut-X axis as intervention targets, the thinking of gut microbiota and its related metabolites in basic studies and clinical prevention and treatment of bone aging-related diseases might be expanded, and its clinical application transformation and development could be innovated.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"57 ","pages":"Article 101064"},"PeriodicalIF":5.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147348551","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":"Mechanistic insights into cartilage-sensory nerve crosstalk in osteoarthritis progression","authors":"Huan Meng ,&nbsp;Junxuan Ma ,&nbsp;Line Kawtharany ,&nbsp;Rui Yue ,&nbsp;Chunyi Wen ,&nbsp;Sibylle Grad ,&nbsp;Olivier Chassande ,&nbsp;Zhen Li","doi":"10.1016/j.jot.2026.101083","DOIUrl":"10.1016/j.jot.2026.101083","url":null,"abstract":"<div><div>Osteoarthritis (OA) pain arises from dynamic crosstalk between degraded cartilage and sensitized sensory nerves. Cartilage-derived signals, including nerve growth factor (NGF), pro-inflammatory cytokines, and matrix-degrading enzymes, promote nerve sprouting and hyperexcitability. While sensory afferents release neuropeptides that further amplify inflammation and cartilage degeneration. Altered joint mechanics additionally activate mechanosensitive ion channels, linking biomechanical stress to nociceptive signaling. This review summarizes current knowledge on cartilage–sensory nerve interactions in OA and their contribution to pain progression. We discuss key molecular mediators, biomarkers, and therapeutic targets, and provide an overview of <em>in vivo</em>, <em>in vitro</em>, and <em>ex vivo</em> model platforms for studying cartilage–sensory nerve crosstalk, highlighting emerging predictive systems for mechanistic and translational research. Together, these insights support the development of mechanism-based pain phenotyping and personalized therapeutic strategies for OA.</div></div><div><h3>Core Take-Home Messages and Clinical Significance</h3><div><ul><li><span>•</span><span><div>Cartilage actively contributes to OA pain by engaging in bidirectional crosstalk with sensory nerves.</div></span></li><li><span>•</span><span><div>Inflammatory mediators, neuropeptides, and mechanosensitive ion channels form an integrated network driving OA pain.</div></span></li><li><span>•</span><span><div>Predictive <em>in vitro</em> and <em>ex vivo</em> models provide tractable platforms to study cartilage–sensory nerve crosstalk and support translational pain research.</div></span></li><li><span>•</span><span><div>Mechanism-linked neural, inflammatory and mechanosensitive biomarkers enable OA pain phenotyping beyond structural severity.</div></span></li></ul></div></div><div><h3>The Translational Potential of this Article</h3><div>This review highlights cartilage–sensory nerve crosstalk as a key mechanism underlying osteoarthritis pain, moving beyond a structure-centric view of disease progression. Mechanistic insights into neuroinflammatory and mechanosensitive pathways support the development of biomarkers for pain phenotyping and patient stratification. These insights have direct implications for clinical trial design and interpretation, particularly in addressing discordance between structural and symptomatic outcomes.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"57 ","pages":"Article 101083"},"PeriodicalIF":5.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147540216","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":"Targeted knockdown of Piezo1 in synovial macrophages attenuates osteoarthritis development","authors":"Zijian Yan ,&nbsp;Dengying Wu ,&nbsp;Haiyue Zhao ,&nbsp;Haitao Guan ,&nbsp;Jianpeng Chen ,&nbsp;Chengbin Huang ,&nbsp;Xuankuai Chen ,&nbsp;Xiangtian Deng ,&nbsp;Jinglue Hu ,&nbsp;Juan Wang ,&nbsp;Yingze Zhang","doi":"10.1016/j.jot.2026.101053","DOIUrl":"10.1016/j.jot.2026.101053","url":null,"abstract":"<div><h3>Objective</h3><div>Osteoarthritis (OA) is a prevalent degenerative joint disease worldwide. Emerging therapies targeting the crosstalk between immune/inflammatory cells and chondrocytes have shown promise. Macrophage phenotypic reprogramming represents a potential therapeutic strategy, yet the molecular mechanisms by which mechanical signals regulate macrophage plasticity remain unclear. This study aimed to investigate the role of the mechanosensitive ion channel Piezo1 in synovial macrophage polarization and its contribution to OA pathogenesis.</div></div><div><h3>Methods</h3><div>Histological analyses were performed on synovial tissues from human OA patients and OA mouse models to assess Piezo1 expression in macrophages. Conditional Piezo1 knockout in macrophages was established in mice to evaluate its effect on OA progression. <em>In vitro</em> and <em>in vivo</em> experiments were conducted to explore the impact of Piezo1 deletion on macrophage polarization and chondrocyte metabolism. Mechanistic studies investigated the involvement of the DRP1-cGAS-STING axis in Piezo1-mediated inflammasome activation. Furthermore, mannose-modified liposomes carrying Si-Piezo1 were constructed to selectively target and inhibit Piezo1 expression in synovial macrophages.</div></div><div><h3>Results</h3><div>Piezo1 expression was significantly upregulated in synovial macrophages from OA joints compared to healthy joints. Macrophage-specific deletion of Piezo1 markedly alleviated OA symptoms and promoted chondrocyte anabolism. Mechanistically, Piezo1 facilitated M1 macrophage polarization by activating the NLRP3 inflammasome via the DRP1-cGAS-STING pathway, which in turn accelerated chondrocyte senescence and degeneration. Targeted delivery of Si-Piezo1 nanoparticles effectively suppressed Piezo1 expression in synovial macrophages, reduced the proportion of M1 macrophages, and alleviated OA progression <em>in vivo</em>.</div></div><div><h3>Conclusion</h3><div>Piezo1 plays a critical role in regulating synovial macrophage polarization through mechanotransduction, thereby promoting OA progression. Targeted inhibition of Piezo1 using mannose-modified nanoparticles provides a promising therapeutic strategy for OA treatment.</div></div><div><h3>Translational potential</h3><div>By offering experimental evidence on the role and mechanism of Piezo1 in OA synovium, this study underscores the potential of Man-LNP@Si-Piezo1 as a therapeutic strategy for OA.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"57 ","pages":"Article 101053"},"PeriodicalIF":5.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147355396","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 scaffold-free cartilage construct fabricated using a bio 3D printer accelerates critical-size bone defect regeneration","authors":"Hiromu Yoshizato ,&nbsp;Daiki Murata ,&nbsp;Shohei Kashimoto ,&nbsp;Toshihiro Nonaka ,&nbsp;Ryota Fujimoto ,&nbsp;Yukiko Nagaishi ,&nbsp;Manabu Itoh ,&nbsp;Tadatsugu Morimoto ,&nbsp;Koichi Nakayama","doi":"10.1016/j.jot.2025.101033","DOIUrl":"10.1016/j.jot.2025.101033","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Critical-size bone defects (CSD), often resulting from trauma or tumour resection, represent a challenging clinical condition that is difficult to treat. Although autologous bone grafting is a common treatment, limitations such as donor site morbidity necessitate the development of novel therapeutic strategies. Approaches that mimic endochondral ossification, the natural process of bone development and healing, are increasingly recognised for their bone regenerative potential. The combination of mesenchymal stem cells and scaffolds, used in many bone regeneration studies, has drawbacks, such as scaffold-derived complications including chronic inflammation and fibrosis. To overcome these issues, we used a bio-three-dimensional (3D) printer that enables the fabrication of scaffold-free 3D cellular constructs. This study aimed to establish a novel therapeutic strategy for CSD by generating scaffold-free cartilage constructs from rat adipose tissue-derived mesenchymal stromal cells (rAT-MSCs) and evaluating their regenerative potential.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Materials and methods&lt;/h3&gt;&lt;div&gt;Scaffold-free cellular constructs were fabricated using rAT-MSCs. Cartilage constructs were generated by chondrogenic induction. A 5-mm CSD was created in the diaphysis of the rat femur. Three experimental groups were established: a Defect group (n = 9), in which no material was implanted into the defect; an MSC group (n = 9), in which undifferentiated constructs were implanted into the defect; and an MSC-Ch (AT-MSC-derived chondrocyte) group (n = 9), in which cartilage constructs were implanted into the defect. Computed tomography (CT) and histological analyses were performed at 6 and 12 weeks post-implantation.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;CT scans showed significantly higher bone volume/total volume ratios in the MSC-Ch group than in the Defect and MSC groups at 6 and 12 weeks (&lt;em&gt;p&lt;/em&gt; &lt; 0.01). Histologically, the MSC-Ch group exhibited robust formation of new cortical and cancellous bone, continuous with native bone margins, leading to bone bridging. In contrast, the Defect and MSC groups demonstrated new bone formation confined to the periphery of the defect, with the central regions predominantly occupied by adipose and fibrous tissues. Histological scoring supported these findings, with the MSC-Ch group achieving significantly higher scores than the Defect and MSC groups at both time points (&lt;em&gt;p&lt;/em&gt; &lt; 0.05).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;Implantation of scaffold-free cartilage constructs derived from rAT-MSCs effectively promoted CSD healing. To the best of our knowledge, this is the first study to successfully regenerate a long bone CSD using AT-MSCs as the cell source by mimicking the endochondral ossification pathway. However, further studies using larger animal models are required to validate and translate these findings.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;The translational potential of this article&lt;/h3&gt;&lt;div&gt;Fabri","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"57 ","pages":"Article 101033"},"PeriodicalIF":5.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147377900","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":"Silencing SFRP1 in bone mesenchymal stem cells alleviates pediatric B-ALL-driven bone loss by activating Wnt/β-catenin signaling","authors":"Mengxia Li ,&nbsp;Xu He ,&nbsp;Xingzhi Liu ,&nbsp;Mimi Chen ,&nbsp;Qian Sun ,&nbsp;Ronghui Yu ,&nbsp;Wendong Liu ,&nbsp;Qi Wang ,&nbsp;Guanghao Su ,&nbsp;Qin Shi ,&nbsp;Xiaodong Wang","doi":"10.1016/j.jot.2026.101071","DOIUrl":"10.1016/j.jot.2026.101071","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Bone loss is the most common skeletal complication of childhood acute lymphoblastic leukemia (ALL) and seriously affects the long-term survival quality of children. However, the mechanisms behind bone loss are complicated and need to be elucidated. This study seeks to examine the principal parameters influencing the osteogenic development of bone marrow mesenchymal stem cells (BMSCs) in pediatric patients with B-cell acute lymphoblastic leukemia (B-ALL) experiencing bone loss, and to identify viable ways for alleviating bone loss.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Firstly, bone mass of adolescent B-ALL patients and mice were evaluated with aged-matched cohorts. Then, human BMSCs (hBMSCs) were isolated from pediatric B-ALL patients and characterized by Flow Cytometry Assay (FCA). ALP, ARS, Oil Red O and toluidine blue staining were used to evaluate the trilineage differentiation of hBMSCs. Integrated RNA-seq and proteomic analyses were employed to identify differentially target osteogenic regulators in B-ALL-derived hBMSCs. On the based that secreted frizzled-related protein 1 (SFRP1) was demonstrated to be a regulator on B-ALL BMSC osteogenesis, BMSC-targeted liposomal nanocarriers were engineered to encapsulate lentiviral particles carrying therapeutic shSFRP1 RNA and grafted with E7 peptide (shSFRP1@Lipo-E7), enabling cell-specific gene silencing in BMSCs. Subsequently, shSFRP1@Lipo-E7 was delivered into B-ALL mice by tail vein injection and bone quality were evaluated by mico-CT and histomorphometric analysis.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Adolescent B-ALL patients exhibited significant vertebral bone loss, with 33.8% of patients affected. In B-ALL mice, BMD and newbone formation were markedly reduced, while osteoclast activity increased. An increased expression of SFRP1 was identified to impair osteogenesis of BMSCs from B-ALL patients. Consequently, a BMSC-targeted nanoplatform, E7 peptide-modified liposomes containing lentiviral shSFRP1 (shSFRP1@Lipo-E7) was constructed successfully. As anticipated, shSFRP1@Lipo-E7 effectively suppressed SFRP1 expression in trabecular osteoblasts and rescued B-ALL mice from bone loss, supported by significantly increasing BMD and improved trabecular structure. Both &lt;em&gt;in vitro&lt;/em&gt; and vivo studies evidenced that silencing of SFRP1 activated Wnt/β-catenin signaling to promote BMSC osteogenesis and bone formation in B-ALL mice.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;High SFRP1 expression in B-ALL BMSCs suppresses osteogenesis and contributes to bone loss in B-ALL cohorts by inhibiting Wnt/β-catenin signaling, which afford a potential translatable target to reprogram bone homeostasis and prevent bone fragility in ALL patients.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;The Translational Potential of this Article&lt;/h3&gt;&lt;div&gt;Given the negative correlation between SFRP1 overexpression in BMSCs of pediatric B-ALL related bone mass loss, precisely targeting SFRP1 in MSCs for intervention holds prom","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"57 ","pages":"Article 101071"},"PeriodicalIF":5.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147540217","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}