{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T19:08:02Z","timestamp":1784401682356,"version":"3.55.0"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T00:00:00Z","timestamp":1756857600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>Post-traumatic osteoarthritis (PTOA) is a degenerative joint disease secondary to joint trauma, such as anterior cruciate ligament (ACL) injury. Our previous study found that the mechanosensitive protein ANTXR1 is involved in the regulation of bone homeostasis, however, whether ANTXR1 is involved in the regulation of cartilage homeostasis in PTOA is unclear. In this study, we focused on the expression of the mechanosensitive protein ANTXR1 in cartilage homeostasis and explored its role in the initiation and progression of PTOA. To investigate the effects of treadmill exercise on bone-cartilage homeostasis, we established models using different exercise intensities (20%, 40%, 60%, 80% of maximal oxygen uptake, VO<jats:sub>2<\/jats:sub>max). Histological staining (Hematoxylin and Eosin, HE) and micro-computed tomography (micro-CT) revealed that moderate-intensity exercise (40%\u201360% VO<jats:sub>2<\/jats:sub>max) effectively promoted bone-cartilage health compared to controls. Conversely, prolonged high-intensity exercise (8 weeks, 80% VO<jats:sub>2<\/jats:sub>max) demonstrated potentially deleterious effects on cartilage homeostasis. Immunofluorescence staining indicated that, compared to the sedentary group, both ANTXR1 protein expression in the knee cartilage was reduced across intervention groups, with expression levels progressively declining as exercise intensity increased. Notably, ANTXR1 and exhibited significantly higher expression in bone tissue compared to cartilage tissue. Bioinformatic analysis identified LRP6 as a potential target protein of ANTXR1. Furthermore, utilizing a post-traumatic osteoarthritis (PTOA) animal model, we explored the potential role of ANTXR1 in cartilage homeostasis and revealed that both ANTXR1 and LRP6 protein expression were significantly upregulated in the degenerating cartilage of PTOA rats. This study is the first to elucidate the dual roles of ANTXR1 in mechano-signaling and cartilage metabolic homeostasis, providing a molecular basis for developing ANTXR1-targeting inhibitors for PTOA treatment.<\/jats:p>","DOI":"10.3389\/fcell.2025.1625333","type":"journal-article","created":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T05:38:13Z","timestamp":1756877893000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["The mechanosensitive protein ANTXR1 is involved in maintaining cartilage homeostasis in post-traumatic osteoarthritis"],"prefix":"10.3389","volume":"13","author":[{"given":"Zhuangzhuang","family":"Miao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjie","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengfei","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinghao","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahang","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajie","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuchang","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongying","family":"Jing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"449","DOI":"10.2519\/jospt.2018.7569","article-title":"Physical impairments in Adults with Ankle osteoarthritis: a systematic review and Meta-analysis","volume":"48","author":"AL-Mahrouqi","year":"2018","journal-title":"J. Orthop. Sports Phys. Ther."},{"key":"B2","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1159\/000213866","article-title":"Do subchondral bone changes exacerbate or precede articular cartilage destruction in osteoarthritis of the elderly?","volume":"43","author":"Bailey","year":"1997","journal-title":"Gerontology"},{"key":"B3","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1016\/s0889-857x(03)00061-9","article-title":"Microfractures and microcracks in subchondral bone: are they relevant to osteoarthrosis?","volume":"29","author":"Burr","year":"2003","journal-title":"Rheum. Dis. Clin. North Am."},{"key":"B4","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1136\/annrheumdis-2011-200557","article-title":"Autophagy activation by rapamycin reduces severity of experimental osteoarthritis","volume":"71","author":"Caram\u00e9S","year":"2012","journal-title":"Ann. Rheum. Dis."},{"key":"B5","doi-asserted-by":"publisher","first-page":"826","DOI":"10.1002\/acr.23086","article-title":"Knee Pain and structural damage as Risk factors for incident Widespread Pain: data from the Multicenter osteoarthritis study","volume":"69","author":"Carlesso","year":"2017","journal-title":"Arthritis Care Res. Hob."},{"key":"B6","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1007\/s12178-011-9088-5","article-title":"Risk factors for incident osteoarthritis of the hip and knee","volume":"4","author":"Chaganti","year":"2011","journal-title":"Curr. Rev. Musculoskelet. Med."},{"key":"B7","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1016\/j.apsb.2024.12.008","article-title":"Nanoengineered cargo with targeted in vivo Foxo3 gene editing modulated mitophagy of chondrocytes to alleviate osteoarthritis","volume":"15","author":"Chen","year":"2025","journal-title":"Acta Pharm. Sin. B"},{"key":"B8","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1111\/nyas.13261","article-title":"The role of subchondral bone damage in post-traumatic osteoarthritis","volume":"1383","author":"Coughlin","year":"2016","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"B10","doi-asserted-by":"publisher","first-page":"101658","DOI":"10.1016\/j.bonr.2023.101658","article-title":"Post-traumatic osteoarthritis: a review of pathogenic mechanisms and novel targets for mitigation","volume":"18","author":"Dilley","year":"2023","journal-title":"Bone Rep."},{"key":"B11","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/j.actbio.2023.01.006","article-title":"ANTXR1 as a potential sensor of extracellular mechanical cues","volume":"158","author":"Feng","year":"2023","journal-title":"Acta Biomater."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1554","DOI":"10.1136\/bjsports-2015-095424","article-title":"Exercise for osteoarthritis of the knee: a Cochrane systematic review","volume":"49","author":"Fransen","year":"2015","journal-title":"Br. J. Sports Med."},{"key":"B13","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1080\/14728222.2023.2185133","article-title":"Emerging therapeutic targets for osteoarthritis","volume":"27","author":"Hadzic","year":"2023","journal-title":"Expert Opin. Ther. Targets"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1227","DOI":"10.1002\/jor.24791","article-title":"Effects of body weight-supported treadmill training on cartilage-subchondral bone unit in the rat model of posttraumatic osteoarthritis","volume":"39","author":"Hao","year":"2021","journal-title":"J. Orthop. Res."},{"key":"B15","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1038\/s41413-025-00414-3","article-title":"LATS1-modulated ZBTB20 perturbing cartilage matrix homeostasis contributes to early-stage osteoarthritis","volume":"13","author":"Hao","year":"2025","journal-title":"Bone Res."},{"key":"B16","doi-asserted-by":"publisher","first-page":"115573","DOI":"10.1016\/j.bone.2020.115573","article-title":"Irisin inhibits osteocyte apoptosis by activating the Erk signaling pathway in vitro and attenuates ALCT-induced osteoarthritis in mice","volume":"141","author":"He","year":"2020","journal-title":"Bone"},{"key":"B17","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1186\/s13018-019-1180-3","article-title":"Managing of post-traumatic knee arthritis by total knee arthroplasty: case series of 15 patients and literature review","volume":"14","author":"Kornah","year":"2019","journal-title":"J. Orthop. Surg. Res."},{"key":"B18","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1038\/s41584-024-01102-y","article-title":"Molecular biomarker approaches to prevention of post-traumatic osteoarthritis","volume":"20","author":"Kraus","year":"2024","journal-title":"Nat. Rev. Rheumatol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1977","DOI":"10.1038\/s41598-017-02126-z","article-title":"Effects of treadmill running with different intensity on rat subchondral bone","volume":"7","author":"Li","year":"2017","journal-title":"Sci. Rep."},{"key":"B20","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1038\/s43587-021-00050-6","article-title":"Exosomal transfer of osteoclast-derived miRNAs to chondrocytes contributes to osteoarthritis progression","volume":"1","author":"Liu","year":"2021","journal-title":"Nat. Aging"},{"key":"B21","doi-asserted-by":"publisher","first-page":"e31214","DOI":"10.1002\/jcp.31214","article-title":"Mechanical strain regulates osteogenesis via Antxr1\/LncRNA H19\/Wnt\/\u03b2-catenin axis","volume":"239","author":"Liu","year":"2024","journal-title":"J. Cell Physiol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1613","DOI":"10.1002\/art.30311","article-title":"Transcriptome-wide gene regulation by gentle treadmill walking during the progression of monoiodoacetate-induced arthritis","volume":"63","author":"Nam","year":"2011","journal-title":"Arthritis Rheum."},{"key":"B23","doi-asserted-by":"publisher","first-page":"6173","DOI":"10.1038\/s41467-023-41836-z","article-title":"The USP46 complex deubiquitylates LRP6 to promote Wnt\/\u03b2-catenin signaling","volume":"14","author":"Ng","year":"2023","journal-title":"Nat. Commun."},{"key":"B24","doi-asserted-by":"publisher","first-page":"R150","DOI":"10.1186\/ar4333","article-title":"Impact of extracellular matrix derived from osteoarthritis subchondral bone osteoblasts on osteocytes: role of integrin\u03b21 and focal adhesion kinase signaling cues","volume":"15","author":"Prasadam","year":"2013","journal-title":"Arthritis Res. Ther."},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1002\/0471140856.tx2302s52","article-title":"Use of zinc finger nuclease technology to knock out efflux transporters in C2BBe1 cells","author":"Pratt","year":"2012","journal-title":"Curr. Protoc. Toxicol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1016\/0531-5565(95)02032-2","article-title":"Oxygen consumption in adult and AGED C57BL\/6J mice during acute treadmill exercise of different intensity","volume":"31","author":"Schefer","year":"1996","journal-title":"Exp. Gerontol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"3079","DOI":"10.21037\/jgo-21-764","article-title":"ANTXR1 as a potential prognostic biomarker for hepatitis B virus-related hepatocellular carcinoma identified by a weighted gene correlation network analysis","volume":"12","author":"Si","year":"2021","journal-title":"J. Gastrointest. Oncol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1468","DOI":"10.1002\/1873-3468.15106","article-title":"Ablation of LRP6 in alpha-smooth muscle actin-expressing cells abrogates lung inflammation and fibrosis upon bleomycin-induced lung injury","volume":"599","author":"Sung","year":"2025","journal-title":"FEBS Lett."},{"key":"B29","doi-asserted-by":"publisher","first-page":"103535","DOI":"10.1016\/j.redox.2025.103535","article-title":"Swimming exercise induces redox-lipid crosstalk to ameliorate osteoarthritis progression","volume":"81","author":"Wu","year":"2025","journal-title":"Redox Biol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1038\/s41392-023-01330-w","article-title":"Osteoarthritis: pathogenic signaling pathways and therapeutic targets","volume":"8","author":"Yao","year":"2023","journal-title":"Signal Transduct. Target Ther."},{"key":"B31","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1146\/annurev.biochem.75.103004.142728","article-title":"Anthrax toxin: receptor binding, internalization, pore formation, and translocation","volume":"76","author":"Young","year":"2007","journal-title":"Annu. Rev. Biochem."},{"key":"B32","doi-asserted-by":"publisher","first-page":"5720360","DOI":"10.1155\/2020\/5720360","article-title":"Biochemical Signals mediate the crosstalk between cartilage and bone in osteoarthritis","volume":"2020","author":"Zhou","year":"2020","journal-title":"Biomed. Res. Int."},{"key":"B33","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1186\/s12938-021-00949-6","article-title":"Moderate-intensity treadmill running relieves motion-induced post-traumatic osteoarthritis mice by up-regulating the expression of lncRNA H19","volume":"20","author":"Zhou","year":"2021","journal-title":"Biomed. Eng. Online"},{"key":"B34","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/j.ncrna.2024.07.005","article-title":"Mechanosensitive lncRNA H19 promotes chondrocyte autophagy, but not pyroptosis, by targeting miR-148a in post-traumatic osteoarthritis","volume":"10","author":"Zhou","year":"2025","journal-title":"Noncoding RNA Res."}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2025.1625333\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T05:38:14Z","timestamp":1756877894000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2025.1625333\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,3]]},"references-count":33,"alternative-id":["10.3389\/fcell.2025.1625333"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2025.1625333","relation":{},"ISSN":["2296-634X"],"issn-type":[{"value":"2296-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,3]]},"article-number":"1625333"}}