Journal of Orthopaedic Translation最新文献

{"title":"Ubiquitination and deubiquitination: Implications for the pathogenesis and treatment of osteoarthritis","authors":"Shibo Su ,&nbsp;Ruijiao Tian ,&nbsp;Yang Jiao ,&nbsp;Shudan Zheng ,&nbsp;Siqiang Liang ,&nbsp;Tianyi Liu ,&nbsp;Ziheng Tian ,&nbsp;Xiuhong Cao ,&nbsp;Yanlong Xing ,&nbsp;Chuqing Ma ,&nbsp;Panli Ni ,&nbsp;Fabiao Yu ,&nbsp;Tongmeng Jiang ,&nbsp;Juan Wang","doi":"10.1016/j.jot.2024.09.011","DOIUrl":"10.1016/j.jot.2024.09.011","url":null,"abstract":"<div><div>Osteoarthritis (OA) is a degenerative disease that affects multiple cells and associated extracellular matrix (ECM). Chondrocytes and chondroextracellular matrix together constitute articular cartilage tissue. Any factors that affect the activity of chondrocytes and destroy the metabolic balance of the chondrocyte ECM will lead to the inability of articular cartilage to perform normal functions. The articular subchondral bone and articular cartilage must be coordinated to resist enough friction and mechanical stress, so the articular subchondral bone lesion will aggravate the articular cartilage defect and vice versa. Synoviocytes, including fibroblast-like synoviocytes (FLSs) and synovial macrophages at the joint, are also important factors that cause low-grade chronic progressive inflammation of OA. Regulation of phenotype transformation of synovial macrophages has become another possible target for the clinical treatment of OA. Ubiquitination and deubiquitination are the main post-translational protein modification pathways in the human body, which are widely involved in multiple signaling pathways and physiological processes. Naturally, they also play a very important regulatory role in the occurrence and development of OA. These effects are summarized in this review, including (A) regulating the aging and apoptosis of chondrocytes, FLSs and osteoblasts; (B) regulation of ECM degradation; (C) regulation of macrophage phenotypic transformation; (D) modulation of skeletal muscle and adipose tissues. Ubiquitination targeting drugs for OA treatment are also listed. Depending on the high efficiency of ubiquitination and deubiquitination, understanding OA-related ubiquitination pathways can help design more efficient drugs to treat OA and provide more potential targets for clinical treatment.</div><div>The Translational Potential of This Article.</div><div>In this paper, the ubiquitination-related pathways in osteoarthritis (OA), including aging, apoptosis and autophagy in chondrocytes, osteoblasts, FLSs and macrophages were investigated. In particular, several ubiquitination-related targets are expected to be effective approaches for OA clinical treatment. In addition, in the process of OA occurrence and development, the complex relationship between the local joint area and other tissues including skeletal muscle and adipose tissue is also discussed. These myokines and adipokines from musculoskeletal tissues are all expected to become efficient targets for OA treatment apart from the joint itself. In addition, those myokines secreted by cardiovascular tissues would show potential therapeutic effects as well. What if altering the contents for these ubiquitination-related targets in the serum through exercise will provide a new idea for OA therapy or prevent OA from deteriorating continuously?</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"49 ","pages":"Pages 156-166"},"PeriodicalIF":5.9,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142421803","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":"Porous metal materials for applications in orthopedic field: A review on mechanisms in bone healing","authors":"Yutong Ma ,&nbsp;Yi Wang ,&nbsp;Shuang Tong ,&nbsp;Yuehan Wang ,&nbsp;Zhuoya Wang ,&nbsp;Rongze Sui ,&nbsp;Ke Yang ,&nbsp;Frank Witte ,&nbsp;Shude Yang","doi":"10.1016/j.jot.2024.08.003","DOIUrl":"10.1016/j.jot.2024.08.003","url":null,"abstract":"<div><h3>Background</h3><div>Porous metal materials have been widely studied for applications in orthopedic field, owing to their excellent features and properties in bone healing. Porous metal materials with different compositions, manufacturing methods, and porosities have been developed. Whereas, the systematic mechanisms on how porous metal materials promote bone healing still remain unclear.</div></div><div><h3>Methods</h3><div>This review is concerned on the porous metal materials from three aspects with accounts of specific mechanisms, inflammatory regulation, angiogenesis and osteogenesis. We place great emphasis on different cells regulated by porous metal materials, including mesenchymal stem cells (MSCs), macrophages, endothelial cells (ECs), etc.</div></div><div><h3>Result</h3><div>The design of porous metal materials is diversified, with its varying pore sizes, porosity material types, modification methods and coatings help researchers create the most experimentally suitable and clinically effective scaffolds. Related signal pathways presented from different functions showed that porous metal materials could change the behavior of cells and the amount of cytokines, achieving good influence on osteogenesis.</div></div><div><h3>Conclusion</h3><div>This article summarizes the current progress achieved in the mechanism of porous metal materials promoting bone healing. By modulating the cellular behavior and physiological status of a spectrum of cellular constituents, such as macrophages, osteoblasts, and osteoclasts, porous metal materials are capable of activating different pathways and releasing regulatory factors, thus exerting pivotal influence on improving the bone healing effect.</div></div><div><h3>The translational potential of this article</h3><div>Porous metal materials play a vital role in the treatment of bone defects. Unfortunately, although an increasing number of studies have been concentrated on the effect of porous metal materials on osteogenesis-related cells, the comprehensive regulation of porous metal materials on the host cell functions during bone regeneration and the related intrinsic mechanisms remain unclear. This review summarizes different design methods for porous metal materials to fabricate the most suitable scaffolds for bone remodeling, and systematically reviews the corresponding mechanisms on inflammation, angiogenesis and osteogenesis of porous metal materials. This review can provide more theoretical framework and innovative optimization for the application of porous metal materials in orthopedics, dentistry, and other areas, thereby advancing their clinical utility and efficacy.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"49 ","pages":"Pages 135-155"},"PeriodicalIF":5.9,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142421802","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":"Unveiling the role of CXCL8/CXCR2 in intervertebral disc degeneration: A path to promising therapeutic strategies","authors":"Pengfei Xue ,&nbsp;Long Lv ,&nbsp;Lei Liu ,&nbsp;Yuzhu Xu ,&nbsp;Chonggang Zhou ,&nbsp;Yuntao Wang","doi":"10.1016/j.jot.2024.08.022","DOIUrl":"10.1016/j.jot.2024.08.022","url":null,"abstract":"<div><h3>Background</h3><div>Intervertebral disc degeneration(IVDD) is the primary etiology of low back pain and radicular pain. Recent studies have found that chemokines play a role in IVDD, but the underlying mechanism is largely unclear.</div></div><div><h3>Methods</h3><div>Bioinformatics analysis was employed to screen CXCL8 as the target gene. The expression levels of CXCL8 and CXCR2 were quantified using RT-qPCR, western blot(WB), immunohistochemistry(IHC), and enzyme-linked immuno-sorbent assay(ELISA). In the IVDD mouse model, X-ray images, Safranin O-fast green staining(SO-FG), IHC, and WB were conducted to assess the therapeutic effects of CXCL8 on IVDD. Reactive oxygen species (ROS) production, apoptosis of nucleus pulposus cells (NPCs), and the involvement of the NF-κB pathway were evaluated through WB, flow cytometry, immunofluorescence(IF), and Tunnel assay.</div></div><div><h3>Results</h3><div>In our study, we observed that CXCL8 emerged as one of the chemokines that were up-regulated in IVDD. The mitigation of extracellular matrix degradation (ECM) and the severity of IVDD were significantly achieved by neutralizing CXCL8 or its receptor CXCR2(SB225002, CXCR2 antagonist). The release of CXCL8 from infiltrated macrophages within intervertebral discs (IVDs) was predominantly observed upon stimulation. CXCL8 exerted its effects on NPCs by inducing apoptosis and ECM degradation through the activation of CXCR2. Specifically, the formation of the CXCL8/CXCR2 complex triggered the NF-κB signaling pathway, resulting in an abnormal increase in intracellular ROS levels and ultimately contributing to the development of IVDD.</div></div><div><h3>Conclusion</h3><div>Our findings suggest that macrophage-derived CXCL8 and subsequent CXCR2 signaling play crucial roles in mediating inflammation, oxidative stress, and apoptosis in IVDD. Targeting the CXCL8/CXCR2 axis may offer promising therapeutic strategies to ameliorate IVDD.</div></div><div><h3>The translational potential of this article</h3><div>This study indicates that CXCL8 can effectively exacerbate the excessive apoptosis and oxidative stress of NPCs through activating the NF-κB pathway. This study may provide new potential targets for preventing and reversing IVDD.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"49 ","pages":"Pages 119-134"},"PeriodicalIF":5.9,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142421808","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":"CD73 alleviates osteoarthritis by maintaining anabolism and suppressing catabolism of chondrocytes extracellular matrix","authors":"Hu Guo ,&nbsp;Zhongyang Lv ,&nbsp;Maochun Wang ,&nbsp;Weitong Li ,&nbsp;Ya Xie ,&nbsp;Zizheng Liu ,&nbsp;Fufei Chen ,&nbsp;Ruiyang Jiang ,&nbsp;Yuan Liu ,&nbsp;Rui Wu ,&nbsp;Jiawei Li ,&nbsp;Ziying Sun ,&nbsp;Guihua Tan ,&nbsp;Dongquan Shi","doi":"10.1016/j.jot.2024.08.014","DOIUrl":"10.1016/j.jot.2024.08.014","url":null,"abstract":"<div><h3>Background</h3><div>Osteoarthritis (OA) is the most common degenerative joint disease, with articular cartilage degeneration as primary manifestation. Intra-articular injection of exogenous liposomal adenosine in mice knee has been shown to alleviate OA progression. However, the role of CD73, the rate-limiting enzyme of extracellular adenosine synthesis, in OA is still unknown.</div></div><div><h3>Methods</h3><div>In this work, we explored the expression changes of adenosine-related molecules via bioinformatic analysis. In addition, the expression level of these molecules was detected in OA cartilage. We also conducted a case–control study to investigate the genetic variants of selected SNPs on genes encoded adenosine-related molecules. To further explore the function of CD73 in chondrocytes, we knocked down the expression of CD73 with small interfering RNA and overexpressed CD73 with the use of lentivirus, and detected the expression of markers for anabolism and catabolism in mouse primary chondrocytes with or without IL-1β treatment. We also conducted <em>in vivo</em> experiments to explore the role of CD73 in OA.</div></div><div><h3>Results</h3><div>We found that the expression of CD73 was upregulated in OA, and the variants of SNP rs2229523 (base A to G) on <em>NT5E</em> (the encoding gene of CD73) were significantly higher in OA population, which might cause the amino acid encoded by this SNP change from threonine to alanine. The original helix structure in the adjacent region of amino acid encoded by SNP rs2229523 would be deconstructed after its mutation. Furthermore, we found that CD73 promoting the expression of Col2a1 but suppressing the expression of Mmp13 expression in mouse primary chondrocytes under inflammatory environment. The overexpression of CD73 attenuated bone remodeling and alleviated cartilage degeneration in DMM mice. Moreover, the physical activities were also improved in DMM mice overexpressed CD73 with the use of adeno-associated virus.</div></div><div><h3>Conclusions</h3><div>The variants of SNP rs2229523 (base A to G) on <em>NT5E</em> were significantly higher in OA population, and CD73 could alleviate OA by maintaining anabolism and suppressing catabolism of chondrocytes extracellular matrix.</div></div><div><h3>The Translational Potential of this Article</h3><div>This work showed that CD73 might be one of the biological therapeutic targets of OA, which would provide a reference for future novel treatment strategy of OA.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"49 ","pages":"Pages 96-106"},"PeriodicalIF":5.9,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142421857","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 senolytic agent ABT263 ameliorates osteoporosis caused by active vitamin D insufficiency through selective clearance of senescent skeletal cells","authors":"Cuicui Yang ,&nbsp;Wanxin Qiao ,&nbsp;Qi Xue ,&nbsp;David Goltzman ,&nbsp;Dengshun Miao ,&nbsp;Zhan Dong","doi":"10.1016/j.jot.2024.08.012","DOIUrl":"10.1016/j.jot.2024.08.012","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background/Objective&lt;/h3&gt;&lt;div&gt;Active vitamin D insufficiency accelerates the development of osteoporosis, with senescent bone cells and the senescence-associated secretory phenotype (SASP) playing crucial roles. This study aimed to investigate whether the senolytic agent ABT263 could correct osteoporosis caused by active vitamin D insufficiency by selectively clearing senescent cells.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Bone marrow mesenchymal stem cells (BM-MSCs) from young and aged mice were treated with ABT263 in vitro, and 1,25(OH)&lt;sub&gt;2&lt;/sub&gt;D-insufficient (Cyp27b1&lt;sup&gt;+/−&lt;/sup&gt;) mice were administered ABT263 in vivo. Cellular, molecular, imaging, and histopathological analyses were performed to compare treated cells and mice with control groups.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;ABT263 induced apoptosis in senescent BM-MSCs by downregulating Bcl2 and upregulating Bax expression. It also induced apoptosis in senescent BM-MSCs from 1,25(OH)&lt;sub&gt;2&lt;/sub&gt;D-insufficient mice. ABT263 administration corrected bone loss caused by 1,25(OH)&lt;sub&gt;2&lt;/sub&gt;D insufficiency by increasing bone density, bone volume, trabecular number, trabecular thickness, and collagen synthesis. It also enhanced osteoblastic bone formation and reduced osteoclastic bone resorption in vivo. ABT263 treatment corrected the impaired osteogenic action of BM-MSCs by promoting their proliferation and osteogenic differentiation. Furthermore, it corrected oxidative stress and DNA damage caused by 1,25(OH)&lt;sub&gt;2&lt;/sub&gt;D insufficiency by increasing SOD-2 and decreasing γ-H2A.X expression. Finally, ABT263 corrected bone cell senescence and SASP caused by 1,25(OH)&lt;sub&gt;2&lt;/sub&gt;D insufficiency by reducing the expression of senescence and SASP-related genes and proteins.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;ABT263 can correct osteoporosis caused by active vitamin D insufficiency by selectively clearing senescent skeletal cells, reducing oxidative stress, DNA damage, and SASP, and promoting bone formation while inhibiting bone resorption. These findings provide new insights into the potential therapeutic application of senolytic agents in the treatment of osteoporosis associated with active vitamin D insufficiency.&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 highlights the therapeutic potential of ABT263, a senolytic compound, in treating osteoporosis caused by active vitamin D insufficiency. By selectively eliminating senescent bone cells and their associated SASP, ABT263 intervention demonstrates the ability to restore bone homeostasis, prevent further bone loss, and promote bone formation. These findings contribute to the growing body of research supporting the use of senolytic therapies for the prevention and treatment of age-related bone disorders. The translational potential of this study lies in the development of novel therapeutic strategies targeting cellular senescence to combat osteoporosis, particularly in cases where vitamin D ","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"49 ","pages":"Pages 107-118"},"PeriodicalIF":5.9,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142421858","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":"From polarity to pathology: Decoding the role of cell orientation in osteoarthritis","authors":"Xiwei Fan ,&nbsp;Louis Jun Ye Ong ,&nbsp;Antonia RuJia Sun ,&nbsp;Indira Prasadam","doi":"10.1016/j.jot.2024.09.004","DOIUrl":"10.1016/j.jot.2024.09.004","url":null,"abstract":"<div><div>Cell polarity refers to the orientation of tissue and organelles within a cell and the direction of its function. It is one of the most critical characteristics of metazoans. The development, growth, and functional tissue distribution are closely related to holistic tissue or organ homeostasis. However, the connection between cell polarity and osteoarthritis (OA) is less well-known. In OA, multiple chondrocyte clusters and tissue disorganisation can be observed in the degraded cartilage tissue. The excessive upregulation of the planar cell polarity (PCP) signalling pathway leads to the loss of cell polarity and organisation in OA progression and aetiology. Recent research has become increasingly aware of the importance of cell polarity and its correlation with OA. Several cell polarity-related treatments have shed light on OA. A thorough understanding of cell polarity and OA would provide more insights for future investigations to treat this worldwide disease.</div></div><div><h3>The translational potential of this article</h3><div>Understanding cell polarity, associated signalling pathways, organelle changes, and cell movement in the development of OA could lead to advances in precision medicine and enhanced treatment strategies for OA patients.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"49 ","pages":"Pages 62-73"},"PeriodicalIF":5.9,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142421800","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 CD163/TWEAK/Fn14 axis: A potential therapeutic target for alleviating inflammatory bone loss","authors":"Ji-kun Qian ,&nbsp;Yuan Ma ,&nbsp;Xuan Huang ,&nbsp;Xiao-ran Li ,&nbsp;Ya-fei Xu ,&nbsp;Zi-ying Liu ,&nbsp;Yuan Gu ,&nbsp;Ke Shen ,&nbsp;Liang-jie Tian ,&nbsp;Yu-tian Wang ,&nbsp;Ning-ning Cheng ,&nbsp;Bing-sheng Yang ,&nbsp;Kui-yuan Huang ,&nbsp;Yu Chai ,&nbsp;Guan-qiao Liu ,&nbsp;Nai-qian Cui ,&nbsp;Song-yun Deng ,&nbsp;Nan Jiang ,&nbsp;Dao-rong Xu ,&nbsp;Bin Yu","doi":"10.1016/j.jot.2024.09.002","DOIUrl":"10.1016/j.jot.2024.09.002","url":null,"abstract":"<div><h3>Objective</h3><div>Osteoclast (OC) over-activation is an important cause of bone loss that is strongly correlated with inflammation. Although the CD163/TWEAK/Fn14 axis has been implicated in several inflammatory pathologies, its contributions to inflammatory bone loss remain poorly understood. This study aimed to evaluate the interaction of the CD163/TWEAK/Fn14 axis with OC in inflammatory bone loss.</div></div><div><h3>Methods</h3><div>To assess the role of CD163 in bone homeostasis, we characterized the bone phenotypes of CD163-deficient mice and their wild-type littermates. CD163 and TWEAK levels were evaluated in the bone marrow of mice with LPS-induced bone loss and individuals with rheumatoid arthritis (RA). Bone mass changes were assessed using uCT and histology following supplementation with recombinant mouse CD163 protein (rCD163) or blockade of TWEAK/Fn14 signaling in CD163-deficient mice and mice with LPS-induced bone loss. The impact of CD163/TWEAK on OC differentiation and bone resorption capacity was analyzed <em>in vitro</em>.</div></div><div><h3>Results</h3><div>CD163 deficiency caused decreased bone mass and increased OC abundance. Lower CD163 expression and higher TWEAK expression were observed in the bone marrow of mice with LPS-induced bone loss and individuals with RA. TWEAK, mainly derived from CD68⁺ macrophages, was responsible for bone loss, and supplementing rCD163 or blocking TWEAK/Fn14 signaling contributed to rescue bone loss. TWEAK/Fn14 synergistically promoted RANKL-dependent OC differentiation and bone resorption capability through downstream mitogen-activated protein kinases (MAPK) signaling, while the pro-osteoclastic effect of TWEAK was suppressed by CD163.</div></div><div><h3>Conclusion</h3><div>Our findings suggest that the CD163/TWEAK/Fn14 axis is a potential therapeutic target for inflammatory bone loss by regulating osteoclastogenesis.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"49 ","pages":"Pages 82-95"},"PeriodicalIF":5.9,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142421807","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":"Development of a standardized and reproducible murine femoral distraction osteogenesis model","authors":"Yuejun Lin ,&nbsp;Zhaowei Jiang ,&nbsp;Jiaming Yang ,&nbsp;Ming Wang ,&nbsp;Haixing Wang ,&nbsp;Xiaoting Zhang ,&nbsp;Xuan Lu ,&nbsp;Shanshan Bai ,&nbsp;Tongzhou Liang ,&nbsp;Botai Li ,&nbsp;Jie Shao ,&nbsp;Lu Zhang ,&nbsp;Dashuang Gao ,&nbsp;Jiajun Chen ,&nbsp;Sien Lin ,&nbsp;Fan Yang ,&nbsp;Gang Li","doi":"10.1016/j.jot.2024.08.001","DOIUrl":"10.1016/j.jot.2024.08.001","url":null,"abstract":"<div><h3>Objective</h3><div>Distraction osteogenesis (DO) has been widely used to treat bone defects as its effectiveness in bone regeneration. Currently, distraction devices for establishing DO models are mainly developed for rats or large animals. However, a mouse DO model is in great need for in-depth mechanistic investigations using various transgenic mice. The current study reports the development of a reproducible murine DO model.</div></div><div><h3>Methods</h3><div>A mini-titanium lengthener was designed and fabricated. The mini-lengthener was applied on the murine femur with four threaded pins using a designed clamp as the drilling and insertion guide. After transverse osteotomy using a Gigli saw, and after 5 days of latency, DO procedures started at 0.3 mm/day for 10 days, and the consolidation period was left for 28 days. The bone formation was monitored by radiography and histology. Potential effects on animal locomotion during DO were also measured by behavior tests.</div></div><div><h3>Results</h3><div>Separated bone segments maintained good alignment during the entire DO phases. New bone formation was found as early as the end of the distraction phase. Active bone remodeling was found between the separated bone segments at late distraction and early consolidation phases. At the mature consolidation phase, bone remodeling was mainly observed in the contact cortical bone. Mice underwent DO procedure did not have significant impairment in their locomotion.</div></div><div><h3>Conclusion</h3><div>We have successfully developed a murine femoral DO model, which may be used to study the biological processes of DO. We also developed the mini-lengthener and the guide clamp to ensure the standardization and reproducibility of the mouse DO model.</div><div>The translational potential of this article: Current study reports the development of a murine femoral DO model. A well-established murine DO model will facilitate further investigations of the biological mechanisms of DO in various transgenic and normal mice.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"49 ","pages":"Pages 74-81"},"PeriodicalIF":5.9,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142421806","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":"An updated overview of the search for biomarkers of osteoporosis based on human proteomics","authors":"Xiong-Yi Wang ,&nbsp;Rui-Zhi Zhang ,&nbsp;Yi-Ke Wang,&nbsp;Sheng Pan,&nbsp;Si-Min Yun,&nbsp;Jun-jie Li,&nbsp;You-Jia Xu","doi":"10.1016/j.jot.2024.08.015","DOIUrl":"10.1016/j.jot.2024.08.015","url":null,"abstract":"<div><div>Osteoporosis is a chronic metabolic disease that increases bone fragility and, leads to severe osteoporotic fractures. In recent years, the use of high-throughput omics to explore physiological and pathological biomarkers related to bone metabolism has gained popularity. In this review, we first briefly review the technical approaches of proteomics. Additionally, we summarize the relevant literature in the last decade to provide a comprehensive overview of advances in human proteomics related to osteoporosis. We describe the specific roles of various proteins related to human bone metabolism, highlighting their potential as biomarkers for risk assessment, early diagnosis and disease course monitoring in osteoporosis. Finally, we outline the main challenges currently faced by human proteomics in the field of osteoporosis and offer suggestions to address these challenges, to inspire the search for novel osteoporosis biomarkers and a foundation for their clinical translation. In conclusion, proteomics is a powerful tool for discovering osteoporosis-related biomarkers, which can not only provide risk assessment, early diagnosis and disease course monitoring, but also reveal the underlying mechanisms of disease and provide key information for personalized treatment.</div></div><div><h3>The translational potential of this article</h3><div>This review provides an insightful summary of recent human-based studies on osteoporosis-associated proteomics, which can aid the search for novel osteoporosis biomarkers based on human proteomics and the clinical translation of research results.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"49 ","pages":"Pages 37-48"},"PeriodicalIF":5.9,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142421859","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":"Mitochondrial destabilization in tendinopathy and potential therapeutic strategies","authors":"Linxiang Cheng ,&nbsp;Qiangqiang Zheng ,&nbsp;Kaijie Qiu ,&nbsp;Dai Fei Elmer Ker ,&nbsp;Xiao Chen ,&nbsp;Zi Yin","doi":"10.1016/j.jot.2024.09.003","DOIUrl":"10.1016/j.jot.2024.09.003","url":null,"abstract":"<div><div>Tendinopathy is a prevalent aging-related disorder characterized by pain, swelling, and impaired function, often resulting from micro-scarring and degeneration caused by overuse or trauma. Current interventions for tendinopathy have limited efficacy, highlighting the need for innovative therapies. Mitochondria play an underappreciated and yet crucial role in tenocytes function, including energy production, redox homeostasis, autophagy, and calcium regulation. Abnormalities in mitochondrial function may lead to cellular senescence. Within this context, this review provides an overview of the physiological functions of mitochondria in tendons and presents current insights into mitochondrial dysfunction in tendinopathy. It also proposes potential therapeutic strategies that focus on targeting mitochondrial health in tenocytes. These strategies include: (1) utilizing reactive oxygen species (ROS) scavengers to mitigate the detrimental effects of aberrant mitochondria, (2) employing mitochondria-protecting agents to reduce the production of dysfunctional mitochondria, and (3) supplementing with exogenous normal mitochondria. In conclusion, mitochondria-targeted therapies hold great promise for restoring mitochondrial function and improving outcomes in patients with tendinopathy.</div><div><strong>The translational potential of this article</strong>: Tendinopathy is challenging to treat effectively due to its poorly understood pathogenesis. This review thoroughly analyzes the role of mitochondria in tenocytes and proposes potential strategies for the mitochondrial treatment of tendinopathy. These findings establish a theoretical basis for future research and the clinical translation of mitochondrial therapy for tendinopathy.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"49 ","pages":"Pages 49-61"},"PeriodicalIF":5.9,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142421860","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}