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However, there has been no substantial progress in the development of FDA-approved drugs for treatment due to a lack of understanding of the specific factors regulating key TMJ-OA molecular mechanisms. Lysyl Oxidase-Like-2 (LOXL2) promotes knee joint cartilage protection and is downregulated in a TMJ-OA animal model. We evaluated the role of LOXL2 in TMJ cartilage, its molecular mechanism, and gene networks using in vivo\n                    <jats:italic>Loxl2<\/jats:italic>\n                    knockout mice (\n                    <jats:italic>Acan-Cre; Loxl2<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>flox\/flox<\/jats:italic>\n                    <\/jats:sup>\n                    ) and ex vivo goat TMJ cartilage. Our results show that\n                    <jats:italic>Loxl2<\/jats:italic>\n                    knockout in mouse cartilage upregulates\n                    <jats:italic>Il1b<\/jats:italic>\n                    ,\n                    <jats:italic>Mmp9<\/jats:italic>\n                    ,\n                    <jats:italic>Mmp13<\/jats:italic>\n                    ,\n                    <jats:italic>Adamts4<\/jats:italic>\n                    , and\n                    <jats:italic>Adamts5<\/jats:italic>\n                    , but reduces the levels of aggrecan and proteoglycan.\n                    <jats:italic>Loxl2<\/jats:italic>\n                    deleted TMJ cartilage show a higher enrichment of inflammatory response, TNFA signaling via NF-\u03baB, extracellular matrix (ECM), and collagen degradation pathway network. Conversely, LOXL2 treatment reduces interleukin-1 beta (IL-1\u03b2)-induced expression of\n                    <jats:italic>Mmp13<\/jats:italic>\n                    , protects mitochondrial function, and ECM from degeneration. Importantly, LOXL2 attenuates IL-1\u03b2-induced chondrocyte apoptosis via the phosphorylation of NF-\u03baB and expression of the pain-related gene\n                    <jats:italic>PTGS2<\/jats:italic>\n                    (encodes COX2). Taken together,\n                    <jats:italic>Loxl2<\/jats:italic>\n                    knockout mice exacerbate TMJ-OA through cartilage\/ECM degradation, mitochondrial dysfunction, chondrocyte apoptosis, and inflammatory gene expression, whereas LOXL2 treatment mitigate these effects.\n                  <\/jats:p>","DOI":"10.1038\/s41368-025-00409-0","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:03:34Z","timestamp":1770163414000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["LOXL2 deletion triggers TMJ osteoarthritis, while overexpression protects it from NF-\u03baB-induced chondrocyte apoptosis"],"prefix":"10.1038","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6963-5889","authenticated-orcid":false,"given":"Rajnikant Dilip","family":"Raut","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0412-7161","authenticated-orcid":false,"given":"Chumki","family":"Choudhury","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9535-3729","authenticated-orcid":false,"given":"Faiza","family":"Ali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7455-6579","authenticated-orcid":false,"given":"Amit kumar","family":"Chakraborty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed Moeeduddin","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6383-9602","authenticated-orcid":false,"given":"Cheyleann","family":"Del Valle Ponce De Leon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5582-4977","authenticated-orcid":false,"given":"Harshal V.","family":"Modh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9661-0289","authenticated-orcid":false,"given":"Pushkar","family":"Mehra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8477-8458","authenticated-orcid":false,"given":"Yuwei","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4602-9258","authenticated-orcid":false,"given":"Alejandro","family":"Almarza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4198-7377","authenticated-orcid":false,"given":"Manish V.","family":"Bais","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,4]]},"reference":[{"key":"409_CR1","doi-asserted-by":"publisher","first-page":"2693","DOI":"10.1056\/NEJMra0802472","volume":"359","author":"SJ Scrivani","year":"2008","unstructured":"Scrivani, S. 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