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It highlights TGF-β as a regulator of cartilage formation, differentiation, and endochondral ossification, and summarizes evidence that TGF-β inhibition may reduce ectopic bone formation, supporting preventive and therapeutic targeting of TGF-β signaling.",{"@graph":14,"@context":72},[15,34,55],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & Report",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/tgf-signaling-in-heterotopic-ossification-the-pathogenesis-and-the-target-for-its-treatment/442670/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/tgf-signaling-in-heterotopic-ossification-the-pathogenesis-and-the-target-for-its-treatment/442670.png","ImageObject",300,407,{"name":42,"@type":43},"awa","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-01","2026-09-29",true,{"@type":52,"interactionType":53,"userInteractionCount":26},"InteractionCounter",{"@type":54},"ViewAction",{"@type":56,"mainEntity":57},"FAQPage",[58,64,68],{"name":59,"@type":60,"acceptedAnswer":61},"What is heterotopic ossification (HO) and how is it classified?","Question",{"text":62,"@type":63},"HO is bone formation in non-skeletal tissues triggered by severe external stimuli. It is commonly categorized into hereditary HO and acquired HO, with acquired HO also known as traumatic HO.","Answer",{"name":65,"@type":60,"acceptedAnswer":66},"Why is TGF-β considered important in HO pathogenesis?",{"text":67,"@type":63},"TGF-β regulates cartilage formation and differentiation and is implicated in endochondral ossification, a common manifestation of HO. Evidence suggests TGF-β can initiate and facilitate multiple stages of HO development.",{"name":69,"@type":60,"acceptedAnswer":70},"How do NSAIDs influence HO prevention after total hip arthroplasty (THA)?",{"text":71,"@type":63},"Modern treatments include NSAIDs for prevention, though debate remains. A Bayesian network meta-analysis of randomized trials suggested celecoxib had the lowest HO incidence, followed by diclofenac and naproxen, while some agents were linked to higher rates.","https://schema.org",{"og:url":32,"og:type":74,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":76,"canonical":32},"index,follow",{"doc_id":78,"site_id":7},442670,1790814598,{"code":4,"msg":81,"data":82},"success",[83,87,91,95,100,105,110,114,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":84,"show_sort_weight":85,"slug":86},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":88,"show_sort_weight":89,"slug":90},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":92,"show_sort_weight":93,"slug":94},"Exam",70,"exam",{"id":96,"doc_module":4,"doc_module_name":25,"category_name":97,"show_sort_weight":98,"slug":99},5,"Comic",60,"comic",{"id":101,"doc_module":4,"doc_module_name":25,"category_name":102,"show_sort_weight":103,"slug":104},6,"Technology",50,"technology",{"id":106,"doc_module":4,"doc_module_name":25,"category_name":107,"show_sort_weight":108,"slug":109},7,"Healthcare",40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":112,"slug":113},8,30,"research-report",{"id":115,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},9,"Religion & Spirituality",20,"religion-spirituality",{"id":117,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":117,"slug":121},"World Cup","world-cup",{"id":123,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":123,"slug":125},10,"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":96,"slug":129},19,"General","general",{"code":4,"msg":81,"data":131},{"doc_id":78,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":111,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":26,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":123,"language":139,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":12,"update_tm":143,"read_time":144},3985747858093,"https://ap-avatar.wpscdn.com/davatar_3d24733baf745e90a7e4bdd5f77d97b2","Huang et al. Journal of Orthopaedic Surgery and Research (2026) 21:8  \n[https://doi.org/10.1186/s13018-025-06542-0](https://doi.org/10.1186/s13018-025-06542-0)  \nJournal of Orthopaedic Surgery and Research  \nREVIEW Open Access  \nTGF-β signaling in heterotopic ossification: the pathogenesis and the target for its treatment  \nZiqiang Huang 1†, Zhenhong He2†, Zhengrong Xiong2, Rong Luo2, Yujian Lan2* and Dingsu Bao2,3*  \nAbstract  \nHeterotopic Ossification (HO) is a complex and multifactorial pathological process characterized by abnormal bone production in areas outside the skeletal system (e. g., inside muscles, periarticular joints, ligaments, and tendons) . This pathology is mainly classified as traumatic and hereditary, and it involves several signaling pathways, such as Wnt/β-catenin, BMP, hedgehog signaling, and transforming growth factor (TGF)-β family. TGF-β plays a key role in the development of HO as an important regulator of cartilage formation and differentiation, and endochondral ossification is a common manifestation of HO. Studies have shown that TGF-β can play an initiating and facilitating role in various stages of HO development, and that ectopic bone formation can be effectively reduced by systemic injection ofTGF-β-neutralizing antibodies. This review summarizes the role ofTGF-β signaling in the pathogenesis of HO and discusses potential preventive and therapeutic means to target TGF-β signaling.  \nKeywords Heterotopic ossification, TGF-β, Molecular mechanism, Therapeutic measures  \nIntroduction  \nHeterotopic ossification (HO) is a process characterized by bone formation in non-skeletal tissues (such as tendons and muscles) induced by severe external stimuli [1]. It is usually categorized into hereditary HO and acquired HO, the latter of which is also known as traumatic HO. A range of factors can contribute to HO, including surgery, nerve injury, severe burns, arthropathy, and genetic disorders [2]. Clinically, HO presents with localized pain, swelling, and stiffness, as well as advanced mature bone  \n†Ziqiang Huang and Zhenhong He are co-first authors who equally contributed to this manuscript.  \n*Correspondence:  \nYujian Lan [lyj13675620780@163.com](lyj13675620780@163.com)[ ](lyj13675620780@163.com)Dingsu Bao [332639420@qq.com](332639420@qq.com)  \n1Ziyang People’s Hospital, Ziyang 641300, Sichuan, China 2Department of Orthopedics, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou 646000, Sichuan, China 3Chengdu University of Traditional Chinese Medicine, Chengdu 610000, Sichuan, China  \nformation that ultimately restricts joint motion, thereby incapacitating people in their daily lives and worsening their quality of life [3]. Current modern medical treatments for HO include surgical resection, radiation therapy, and the use of nonsteroidal anti-inflammatory drugs (NSAIDs) [4].  \nHO following total hip arthroplasty (THA) is commonly managed with postoperative NSAIDs for analgesia and HO prevention. Although NSAID-based strategies offer a convenient and potentially safer option, debate remains. A Bayesian network meta-analysis of randomized trials comparing all available NSAIDs for HO prevention after THA found that celecoxib was associated with the lowest HO incidence, followed by diclofenac and naproxen. By contrast, tofacitinib, acetylsalicylic acid (aspirin), and meloxicam were linked to higher HO rates post-THA. Subgroup analyses comparing COX-2–selective versus nonselective NSAIDs showed no consistent statistically significant differences [5]. Further metaanalysis indicated similar efficacy between selective and nonselective NSAIDs for HO prevention after THA [6].  \n© The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the ori","cbCaihr4dAhXavDt","https://ap.wps.com/l/cbCaihr4dAhXavDt","pdf",1420555,"English","# Abstract\n# Introduction\n## HO definition and classification\n## Factors and clinical features\n## Current treatments and NSAID evidence\n# HO development and involved signaling pathways","[{\"question\":\"What is heterotopic ossification (HO) and how is it classified?\",\"answer\":\"HO is bone formation in non-skeletal tissues triggered by severe external stimuli. It is commonly categorized into hereditary HO and acquired HO, with acquired HO also known as traumatic HO.\"},{\"question\":\"Why is TGF-β considered important in HO pathogenesis?\",\"answer\":\"TGF-β regulates cartilage formation and differentiation and is implicated in endochondral ossification, a common manifestation of HO. Evidence suggests TGF-β can initiate and facilitate multiple stages of HO development.\"},{\"question\":\"How do NSAIDs influence HO prevention after total hip arthroplasty (THA)?\",\"answer\":\"Modern treatments include NSAIDs for prevention, though debate remains. A Bayesian network meta-analysis of randomized trials suggested celecoxib had the lowest HO incidence, followed by diclofenac and naproxen, while some agents were linked to higher rates.\"}]","TGF-β signaling in heterotopic ossification: the pathogenesis and the target for its treatment | PDF",1790701145,25]