{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:08:06Z","timestamp":1791378486193,"version":"4.3.2"},"reference-count":39,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,12,22]],"date-time":"2024-12-22T00:00:00Z","timestamp":1734825600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100011912","name":"Taipei Veterans General Hospital","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011912","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Excessive mechanical overloading of articular cartilage caused by excessive exercise or severe trauma is considered a critical trigger in the development of osteoarthritis (OA). However, the available clinical theranostic molecular targets and underlying mechanisms still require more elucidation. Here, we aimed to examine the possibility that bone morphogenetic proteins (BMPs) serve as molecular targets in rat cartilages and human chondrocytes under conditions of excessive mechanical overloading. Two rat models involving high\u2010intensity running training and surgery for destabilization of medial meniscus, along with a cell model subjected to cyclic tensile strain, were established to simulate and investigate excessive mechanical overloading effects on cartilages\/chondrocytes. We employed various methods, including immunohistochemistry, real\u2010time polymerase chain reaction, western blot analysis, and enzyme\u2010linked immunosorbent assay, to evaluate the expression, secretion, phosphorylation, and nuclear translocation of mRNA\/proteins in cartilages and chondrocytes. Our findings revealed a simultaneous upregulation of BMP\u20102 and downregulation of BMP\u20104 in degenerated and inflamed cartilages and chondrocytes under excessive mechanical overloading. Furthermore, toll\u2010like receptor 2 and nuclear factor kappa B\u2010p50\/p65 subunits signaling were identified as regulators governing this distinct expression pattern. Treatment with recombinant BMP\u20102 and\/or BMP\u20104 proteins significantly ameliorated cartilage degeneration and chondrocyte inflammation induced by excessive mechanical overloading. These results strongly suggest that BMP\u20102 upregulation and BMP\u20104 downregulation might represent mechanisms for self\u2010rescue and degeneration in damaged cartilage\/chondrocytes, respectively. Our findings advance new insights that BMP\u20102\/\u20104 might be potential molecular targets for excessive mechanical overloading\u2010caused OA development and should be taken into account in future clinical applications.<\/jats:p>","DOI":"10.1002\/jcp.31509","type":"journal-article","created":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T06:06:39Z","timestamp":1734933999000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Potential Role of Bone Morphogenetic Protein\u20102\/\u20104 in Excessive Mechanical Overloading\u2010Initiated Joint Degeneration"],"prefix":"10.1002","volume":"240","author":[{"given":"Rong\u2010Ze","family":"Hsieh","sequence":"first","affiliation":[{"name":"Department of Medical Research and Development Chiayi Chang Gung Memorial Hospital Chiayi Taiwan"},{"name":"Graduate Institute of Clinical Medical Sciences, College of Medicine Chang Gung University Taoyuan 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