{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T16:18:28Z","timestamp":1792685908657,"version":"4.5.0"},"reference-count":59,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"14","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2023,4,7]]},"abstract":"<jats:p>\n                    Abnormal subchondral bone remodeling featured by overactivated osteoclastogenesis leads to articular cartilage degeneration and osteoarthritis (OA) progression, but the mechanism is unclear. We used lymphocyte cytosolic protein 1 (\n                    <jats:italic>Lcp1<\/jats:italic>\n                    ) knockout mice to suppress subchondral osteoclasts in a mice OA model with anterior cruciate ligament transection (ACLT), and\n                    <jats:italic>Lcp1<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice showed decreased bone remodeling in subchondral bone and retarded cartilage degeneration. For mechanisms, the activated osteoclasts in subchondral bone induced type-H vessels and elevated oxygen concentration, which ubiquitylated hypoxia-inducible factor 1 alpha subunit (HIF-1\u03b1) in chondrocytes and led to cartilage degeneration.\n                    <jats:italic>Lcp1<\/jats:italic>\n                    knockout impeded angiogenesis, which maintained hypoxia environment in joints and delayed the OA progression. Stabilization of HIF-1\u03b1 delayed cartilage degeneration, and knockdown of\n                    <jats:italic>Hif1a<\/jats:italic>\n                    abolished the protective effects of\n                    <jats:italic>Lcp1<\/jats:italic>\n                    knockout. Last, we showed that Oroxylin A, an\n                    <jats:italic>Lcp1-<\/jats:italic>\n                    encoded protein\n                    <jats:sc>l<\/jats:sc>\n                    -plastin (LPL) inhibitor, could alleviate OA progression. In conclusion, maintaining hypoxic environment is an attractive strategy for OA treatment.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.abo7868","type":"journal-article","created":{"date-parts":[[2023,4,5]],"date-time":"2023-04-05T13:58:37Z","timestamp":1680703117000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":197,"title":["Maintaining hypoxia environment of subchondral bone alleviates osteoarthritis progression"],"prefix":"10.1126","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2865-149X","authenticated-orcid":true,"given":"Hao","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Orthopedics, Shanghai Changhai Hospital, Naval Medical University, Shanghai 200433, China."},{"name":"Institute of Translational Medicine, Shanghai University, Shanghai 200444, China."},{"name":"Department of Orthopedic, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 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