Journal of Orthopaedic Translation最新文献

{"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":"2025-08-26","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":"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":"2025-08-26","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":"Artificial ligaments in anterior cruciate ligament reconstruction: Coating strategies for PET-based materials","authors":"Zhen Peng ,&nbsp;Xinting Feng ,&nbsp;Jiale Tan ,&nbsp;Chunfeng Song ,&nbsp;Laimeng Song ,&nbsp;Yuting Wu ,&nbsp;Lingyi Yuan ,&nbsp;Jiwu Chen","doi":"10.1016/j.jot.2025.08.006","DOIUrl":"10.1016/j.jot.2025.08.006","url":null,"abstract":"<div><div>Artificial ligaments, as an important implant for Anterior Cruciate Ligament reconstruction (ACLR), offer notable advantages in early return to sport. However, most artificial ligaments currently used in clinical ACLR are made of polyethylene terephthalate (PET), a polymer characterized by a smooth and hydrophobic surface that limits cell adhesion and tissue growth, leading to the formation of fibrous scar tissue at the tendon-bone interface. To address these limitations, various surface coating strategies have been developed, including biocompatible, tissue inductive, osteoconductive, drug delivery, and immunomodulatory coatings. These approaches improve biological performance, promote ligamentization, and enhance integration with host tissues. Additionally, the application of composite functional coatings and smart responsive coatings offers new directions for future research. Despite promising preclinical results, most studies remain at the animal experiment stage, and the underlying mechanisms need further investigation. This review summarizes recent advances in coating strategies for artificial ligaments, highlighting their functional classification, technical development, and potential for clinical translation.</div></div><div><h3>Translational potential statement</h3><div>To address key challenges in the application of artificial ligaments, such as limited biocompatibility and poor tissue integration, it is essential to understand the current research progress. This review provides a comprehensive overview of the coatings used for ligaments, highlighting the promising role of surface modification in enhancing implant performance. It offers valuable insights for improving the clinical success rate of artificial ligaments and their long term effectiveness in ACLR, thus holding significant clinical translational potential.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"55 ","pages":"Pages 22-37"},"PeriodicalIF":5.9,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144895863","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":"Chronic expanding hematomas arising over a decade post primary total hip arthroplasty","authors":"Chuanlong Wu ,&nbsp;Hongyi Wang ,&nbsp;Teng Yu ,&nbsp;Qiyuan Bao ,&nbsp;Junxiang Wen ,&nbsp;Jiong Zhang ,&nbsp;Zhihong Liu ,&nbsp;Jianmin Feng ,&nbsp;Weibin Zhang ,&nbsp;Chuan He","doi":"10.1016/j.jot.2025.03.017","DOIUrl":"10.1016/j.jot.2025.03.017","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Chronic expanding hematoma (CEH) is an infrequent yet serious complication following total hip arthroplasty (THA). Mismanagement of this condition can result in severe consequences. The purpose of this study is to conduct a retrospective analysis of patients who developed CEH after THA at our institution over the past 20 years, complemented by a review of the existing literature. This comprehensive approach aims to contribute valuable clinical insights into the diagnosis and management of CEH.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;In this study, we conducted a retrospective study of patients who had undergone THA within the past two decades and subsequently developed CEH during their follow-up period at our institution. The data collected encompassed fundamental patient demographics, including age, gender, and specifics regarding the primary THA implants. Additionally, we gathered preoperative, postoperative, and follow-up imaging studies. Following the data compilation, a thorough literature review was performed to aggregate and analyze the published cases of CEH occurring post-THA.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Our follow-up data identified five patients who developed CEH more than ten years after undergoing THA. In one case, CEH manifested subsequent to a traumatic event, while the remaining four cases were non-traumatic. The outcomes following revision surgery were heterogeneous: two patients showed no indications of recurrence throughout a least follow-up period of over one year, one patient eventually underwent amputation, and two patients developed periprosthetic joint infection (PJI), an ongoing management challenge. Our literature review revealed nine previously reported cases with similar clinical features. A summary is as follows: &lt;strong&gt;Etiology&lt;/strong&gt;: While often linked to trauma or surgery, a definitive cause is not always present. It is hypothesized that inadequate hemostasis during the initial procedure may contribute to the development of CEH. &lt;strong&gt;Time Course&lt;/strong&gt;: The condition typically evolves slowly over an extended period of years. &lt;strong&gt;Mechanism&lt;/strong&gt;: The underlying mechanism remains unclear. &lt;strong&gt;Diagnosis&lt;/strong&gt;: &lt;strong&gt;MRI&lt;/strong&gt;: T2-weighted sequences exhibits a combination of hypointense and hyperintense signals reflecting a blend of fresh and old blood, indicative of recurrent hemorrhage. Isointense or slightly high signals on T1-weighted sequences. &lt;strong&gt;Histological Features&lt;/strong&gt;: Characterized by three distinct aspects: a peripheral wall densely encapsulated in fibrous tissue; fresh and mobile blood clots; and a central zone of loose connective tissue formation. &lt;strong&gt;Differential Diagnosis&lt;/strong&gt;: Includes inflammatory pseudotumors, hemophilia, and malignant neoplasms, among others. &lt;strong&gt;Treatment&lt;/strong&gt;: The gold standard of care involves complete surgical resection, inclusive of the capsule. Given CEH's propensity for progressive bone r","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"54 ","pages":"Pages 199-213"},"PeriodicalIF":5.9,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863798","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":"Innovative strategies for bone organoid: Synergistic application and exploration of advanced technologies","authors":"Xu Lou ,&nbsp;Qirong Zhou ,&nbsp;Zhenglin Dong ,&nbsp;Long Bai ,&nbsp;Jiacan Su ,&nbsp;Hua Yue","doi":"10.1016/j.jot.2025.07.010","DOIUrl":"10.1016/j.jot.2025.07.010","url":null,"abstract":"<div><div>Bone organoids, as three-dimensional (3D) biomimetic constructs, have emerged as a promising platform for studying bone development, disease modeling, drug screening, and regenerative medicine. This review comprehensively explores innovative strategies driving bone organoid advancements, emphasizing the integration of cutting-edge technologies such as bioprinting, artificial intelligence, assembloids, and gene editing. While 3D bioprinting enhances spatial precision and structural complexity, artificial intelligence accelerates organoid optimization through data-driven approaches. Assembloids enable the assembly of multicellular systems to better replicate bone tissue microenvironments, whereas gene editing refines disease modeling and functional modifications. Despite these advancements, challenges remain, including the lack of vascularization, insufficient mechanical stimulation, and standardization issues across different models. Also, the clinical translation of bone organoids necessitates the establishment of rigorous evaluation frameworks, ethical guidelines, and regulatory policies to ensure their reproducibility and safety. Looking ahead, interdisciplinary convergence will be critical for constructing physiologically relevant “<em>ex vivo</em> skeletal systems”, advancing bone biology, precision medicine, and biomaterial testing. This review highlights the transformative potential of bone organoid technology and its future applications in personalized orthopedics and bone disease intervention.</div></div><div><h3>The Translational Potential of this Article</h3><div>This review provides a comprehensive overview of cutting-edge strategies for constructing bone organoids, emphasizing their integration with advanced technologies such as bioprinting, artificial intelligence, assembloids, and gene editing. By systematically discussing their applications in bone development, disease modeling, drug screening, and regenerative medicine, this article bridges the gap between experimental models and clinical translation. The insights into vascularization, skeletal patterning, and high-throughput screening platforms offer a foundation for developing physiologically relevant bone organoids with enhanced fidelity and functionality. These advancements hold significant potential for accelerating personalized medicine, facilitating preclinical evaluation of therapeutics, and ultimately improving treatment outcomes for skeletal diseases.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"54 ","pages":"Pages 180-198"},"PeriodicalIF":5.9,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144828534","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":"Forkhead box O proteins in chondrocyte aging and diseases.","authors":"Yuchen He, Weihong Zhu, Peter G Alexander, Sophie E Hines, Olivia G Bartholomew, Chunfeng Zhao, Qian Liu, Hang Lin","doi":"10.1016/j.jot.2025.07.011","DOIUrl":"10.1016/j.jot.2025.07.011","url":null,"abstract":"<p><p>As people age, the progressive loss of cartilage integrity occurs, accompanied by a decline in the capacity to repair. This results in decreased resilience and increased susceptibility of cartilage to various physiological stressors, which raises the risk of developing osteoarthritis (OA). Therefore, restoring the regenerative capacity of chondrocytes and slowing down the aging process could be promising therapeutic strategies to mitigate or even reverse age-related joint diseases. Forkhead box class O (FoxO) proteins are a family of transcription factors that play a crucial role in various cellular processes linked to aging. Their significant functions in cell cycle regulation, apoptosis, and resistance to oxidative stress highlight their importance in maintaining cellular homeostasis and promoting longevity. In this review, we introduce the structures and functions of FoxO proteins in chondrocytes, focusing on their spatiotemporal regulation of epigenetics during chondrocyte differentiation stages in different layers. The critical roles of FoxO proteins in maintaining chondrocyte homeostasis are summarized, alongside a discussion of how FoxO dysfunction contributes to aging and OA. Furthermore, therapeutic strategies targeting FoxO proteins to mitigate aging-related cartilage degradation and decelerate OA progression are explored. Finally, potential directions for future research are proposed to deepen the current understanding of FoxO proteins.</p><p><strong>The translational potential of this article: </strong>FoxO transcription factors, especially FoxO1 and FoxO3, are promising therapeutic targets for promoting longevity, stimulating cartilage regeneration, and treating aging-related diseases like OA.</p>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"54 ","pages":"167-179"},"PeriodicalIF":5.9,"publicationDate":"2025-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12357264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144873680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NLRP3 inflammasome impairs fracture repair in Rheumatoid arthritis through RhoA/Rac1-IL1β axis-mediated suppression of osteoblast differentiation.","authors":"Fen Miao, Hanjia Cai, Yue Chen, Ziwei Yan, Ruofan Jin, Yueming Dai, Lu Li, Hua Wang, Yan Xu, Wen Sun","doi":"10.1016/j.jot.2025.07.012","DOIUrl":"10.1016/j.jot.2025.07.012","url":null,"abstract":"<p><strong>Objective: </strong>Rheumatoid arthritis (RA) is often characterized by bone loss and fragility fractures and is a frequent comorbidity. The NLRP3 inflammasome drives inflammatory processes that fundamentally accompany the pathogenesis of RA. However, the role of NLRP3 inflammasome in RA fracture healing remains unclear.</p><p><strong>Methods: </strong>For <i>in vivo</i> analyses, we established tibial fractures in two murine RA models: TNF-transgenic (TNF^Tg) mice and collagen-induced arthritis (CIA). To address the contribution of NLRP3 inflammasome to fracture repair, we generated TNF^Tg; NLRP3^KO mice by deleting the NLRP3 gene in TNF^Tg mice. The effects of TNFα overexpression on osteogenic differentiation were assessed using mesenchymal progenitor cells (MPCs) with or without MCC950. The role of MCC950 in RA fracture repair was investigated using CIA mice.</p><p><strong>Results: </strong>TNF^Tg mice exhibited delayed fracture healing, characterized by decreased callus bone volume and reduced bone mechanical strength. The NLRP3 inflammasome was excessively activated in TNF^Tg mice, leading to elevated expression of NLRP3, pro-Caspase-1, Caspase-1 p20, pro-IL-1β and IL-1β. Moreover, NLRP3 deficiency in TNF^Tg mice significantly mitigated the delayed fracture healing. Mechanistically, TNFα overexpression suppressed osteogenic differentiation of MPCs through NLRP3 inflammasome activation. This process involves RhoA/Rac1-dependent NF-κB signaling that triggers inflammasome assembly, ultimately leading to IL-1β secretion. Notably, MCC950 administration significantly attenuated these pathological effects. Lastly, <i>in vivo</i> MCC950 treatment rescued the delayed fracture healing by reducing NLRP3 inflammasome activation and promoting bone formation in CIA mice.</p><p><strong>Conclusions: </strong>Collectively, these findings suggest that NLRP3 inflammasome activation drives impaired fracture healing in RA through RhoA/Rac1‒IL-1β axis-mediated suppression of osteoblast differentiation, and pharmacologic inhibition with MCC950 effectively rescues delayed fracture healing in RA mouse model.</p><p><strong>The translational potential of this article: </strong>This study provides novel insights into the mechanisms underlying delayed fracture healing in RA and highlights the potential therapeutic benefits of targeting the NLRP3 inflammasome.</p>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"54 ","pages":"152-166"},"PeriodicalIF":5.9,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12357271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144873682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of multi-omics in biomarker discovery, diagnosis, prognosis, and therapeutic monitoring of tissue repair and regeneration processes.","authors":"Jiamei Liu, Liyu Yang, Dongze Liu, Qianlong Wu, Yuanqi Yu, Xiaoming Huang, Jianjun Li, Shengye Liu","doi":"10.1016/j.jot.2025.07.006","DOIUrl":"10.1016/j.jot.2025.07.006","url":null,"abstract":"<p><p>In the last two decades, technological interventions have played a significant role in transforming healthcare with timely diagnosis and novel therapeutic interventions. Advanced technologies such as next-generation sequencing, NMR, mass spectrometry, and non-invasive imaging modalities have made it possible to study biological molecules, cellular processes, and molecular pathways in different diseases. The \"omics revolution\" is another addition that emerged as a powerful tool in elucidating molecular and cellular processes in diseases. Given the profoundly complex nature of tissue repair, it is important to employ the advanced multi-omics technique to elucidate the cellular, molecular, and inflammatory events in damaged tissues. As proven in various other diseases, these integrative omics can provide a systematic and comprehensive understanding of the biology of tissue repair and regeneration. Proteomics and transcriptomics, in particular, have been widely used for the identification and validation of potential biomarkers such as transforming growth factor-beta (TGF-β), vascular endothelial growth factor (VEGF), interleukin 6 (IL-6), and several matrix metalloproteinases (MMPs) which play a key role in the process of tissue repair and regeneration. Metabolomics, such as NMR and spectroscopies, have also shown potential in tracking energy metabolism and oxidative stress during regeneration. This review article presents a comprehensive overview of the latest multi-omics techniques and technologies that provide valuable insights into the complex processes of tissue repair and highlight the possibilities of early diagnosis, biomarker identification, and novel therapeutic interventions for tissue repair and regeneration. Combining data and key findings from multiple omics layers, such as metabolomics, transcriptomics, and genomics, may provide a comprehensive understanding of the mechanisms and pathways that have been implicated in tissue repair and regeneration. This may lead to the identification and validation of robust biomarkers and the development of therapeutic strategies aimed at improving outcomes in patients with chronic and non-healing wounds.</p><p><strong>The translational potential of this article: </strong>This article reviews the application of multi-omics technologies in tissue repair and regeneration, highlighting how the integration of genomics, transcriptomics, proteomics, and metabolomics reveals molecular mechanisms of wound healing. By combining these diverse omics approaches, the findings provide critical insights into novel biomarkers, therapeutic targets, and personalized treatment strategies. This integration allows for a more comprehensive understanding of tissue regeneration, enhancing diagnostic accuracy and treatment monitoring. Ultimately, multi-omics technologies can drive advances in personalized medicine, improving clinical outcomes and offering new avenues for treating tissue repair and regeneration.</p>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"54 ","pages":"131-151"},"PeriodicalIF":5.9,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12356027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144873683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Narirutin mitigates inflammatory arthritis and osteoporosis through modulating macrophage phenotype and osteoclastogenesis.","authors":"Qing Wang, Xiaole Peng, Hao Xu, Yuhu Zhao, Xiaoheng Lu, Chengyao Lu, Qihan Wang, Wei Lu, Qifeng Sheng, Xiaomin Lu, Yaozeng Xu, Dechun Geng","doi":"10.1016/j.jot.2025.07.008","DOIUrl":"10.1016/j.jot.2025.07.008","url":null,"abstract":"<p><strong>Background: </strong>Inflammatory arthritis (IA), exemplified by rheumatoid arthritis (RA), represents a prevalent autoimmune-driven inflammatory bone disorder hallmarked by chronic synovitis and progressive bone erosion, culminating in joint dysfunction and systemic osteoporosis. Narirutin (NRT), a flavonoid glycoside derived from citrus plants, is renowned for its multifaceted bioactivities, including antioxidant, immunomodulatory, and cardioprotective properties. Despite these attributes, the role of NRT in mitigating macrophage-mediated pro-inflammatory activation and osteoclastogenesis within the context of inflammatory arthritis and osteoporosis remains insufficiently elucidated. This study aimed to evaluate the therapeutic potential of NRT in the context of inflammatory arthritis and osteoporosis.</p><p><strong>Methods: </strong>The phenotypic modulation of macrophages and the osteoclastogenic effects of NRT were evaluated using RAW264.7, THP-1 and bone marrow-derived macrophages (BMMs) <i>in vitro</i>. A classical collagen-induced arthritis (CIA) model was established to investigate the therapeutic effects of NRT administration on inflammatory arthritis and osteoporosis. Macrophage phenotypes and the expression of inflammatory mediators were analyzed <i>in vitro</i> and <i>vivo</i>, respectively. High-throughput RNA sequencing and bioinformatics analyses were employed to identify key downstream signaling pathways, which were further validated. Histological staining, micro-CT, and immunehistofluorescence staining were utilized to assess the <i>in vivo</i> amelioration of inflammation and bone destruction. Visceral toxicity was also assessed <i>in vivo</i>.</p><p><strong>Results: </strong>NRT markedly inhibited lipopolysaccharide (LPS)-induced macrophage polarization towards the pro-inflammatory M1 phenotype (CD86⁺), while promoting a shift towards the anti-inflammatory M2 phenotype (CD206+). This was accompanied by a suppression of pro-inflammatory cytokines, including iNOS, TNF, IL-1β, and IL-6, and an upregulation of immunosuppressive mediators such as IL-10 and Arg-1. RNA sequencing revealed that NRT attenuates the activation of the NOD-like receptor signaling pathway and downstream inflammasome activation. Additionally, osteoclast differentiation was also significantly inhibited, as evidenced by the suppression of NF-κB and MAPK signaling pathways. <i>In vivo</i> studies demonstrated that NRT substantially alleviates the severity of inflammatory arthritis and mitigates systemic osteoporosis.</p><p><strong>Conclusion: </strong>These findings demonstrated that NRT mitigates inflammatory arthritis and osteoporosis through modulating macrophage phenotype and osteoclastogenesis <i>via</i> NOD-like receptor signaling pathway induced inflammasome activation and NF-κB and MAPK signaling pathways, respectively.</p><p><strong>The translational potential of this article: </strong>These findings highlight the potential of tar","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"54 ","pages":"115-130"},"PeriodicalIF":5.9,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12356004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144873681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Growth factor independence 1 ameliorates osteoarthritis by inhibiting chondrocyte ferroptosis via inactivation of MAPK signaling pathway","authors":"Xiaoyu Jin ,&nbsp;Xunhao Wang ,&nbsp;Siyu Xu ,&nbsp;Nuo Xu ,&nbsp;Ziwei Wang ,&nbsp;Chunqing Hu ,&nbsp;Wei Liu ,&nbsp;Zhaofeng Zhang ,&nbsp;Xiyu Liu ,&nbsp;Jingjing Fan ,&nbsp;Ruiyang Jiang ,&nbsp;Rui Wu ,&nbsp;Zhongyang Lv ,&nbsp;Dongquan Shi","doi":"10.1016/j.jot.2025.07.003","DOIUrl":"10.1016/j.jot.2025.07.003","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Osteoarthritis (OA) is the most common degenerative joint disease, characterized by cartilage deterioration, which is closely associated with chondrocyte ferroptosis. The aim of this study was to investigate the role and mechanism of previously unexplored gene, growth factor independence 1 (&lt;em&gt;Gfi1&lt;/em&gt;) in chondrocyte ferroptosis, in order to provide a new therapeutic target for OA.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;The expression of ferroptotic hallmarks and Gfi1 were analyzed in human and mice OA cartilages and tert-butyl hydroperoxide (TBHP)-induced primary chondrocytes. Small interfering RNA or overexpression plasmids were used to knock down or overexpress &lt;em&gt;Gfi1&lt;/em&gt; to explore its role in chondrocyte ferroptosis and metabolism. Then, the role of Gfi1 in destabilization of medial meniscus (DMM) surgery-induced mice OA model was investigated with or without the intra-articular injection of adeno-associated virus-overexpressing &lt;em&gt;Gfi1&lt;/em&gt; (AAV-&lt;em&gt;Gfi1&lt;/em&gt;). Furthermore, RNA sequencing analysis was performed to reveal the key downstream pathway of Gfi1 exerting its role in chondrocyte ferroptosis.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;The expression of Gfi1 was significantly decreased, while 4-HNE, a typical lipid peroxidation product, was significantly increased both in damaged human and DMM surgery-induced mice OA cartilages. Consistently, Gfi1 was remarkably downregulated in TBHP-induced ferroptotic chondrocytes. Moreover, &lt;em&gt;Gfi1&lt;/em&gt; knockdown aggravated chondrocyte ferroptosis by elevated levels of ferroptotic hallmarks, including total ROS, lipid ROS and Fe&lt;sup&gt;2+&lt;/sup&gt; accumulation. The upregulation of ferroptotic driver (Cox2, Acsl4) and catabolic marker (Mmp13) and downregulation of ferroptotic suppressors (Gpx4, Fth1, Slc7a11) and anabolic marker (Col II) were also observed in TBHP-induced chondrocytes by &lt;em&gt;Gfi1&lt;/em&gt; knockdown. On the contrary, &lt;em&gt;Gfi1&lt;/em&gt; overexpression showed anti-ferroptotic effect in TBHP-induced chondrocytes. Intra-articular injection of AAV-&lt;em&gt;Gfi1&lt;/em&gt; evidently alleviated cartilage degeneration by resisting ferroptosis and preserving the anabolism-catabolism homeostasis in OA cartilages. Comprehensive evaluation of subchondral bone sclerosis, osteophyte formation, synovitis and behavior performance further validated that &lt;em&gt;Gfi1&lt;/em&gt; overexpression ameliorated OA progression. Mechanistically, MAPK signaling pathway was identified as the key downstream mediator of Gfi1 exerting anti-ferroptotic role in OA.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;Gfi1 is downregulated in OA and its overexpression ameliorates OA progression by inhibiting chondrocyte ferroptosis via inactivation of MAPK signaling pathway.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;The translational potential of this article&lt;/h3&gt;&lt;div&gt;This study identifies Gfi1 as a novel therapeutic anti-ferroptotic target for cartilage degeneration, providing more clues for optimizing OA treatment strategies in clinical practice.&lt;/div&gt;&lt;/di","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"54 ","pages":"Pages 101-114"},"PeriodicalIF":5.9,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144724425","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}