Matches in SemOpenAlex for { <https://semopenalex.org/work/W4362637048> ?p ?o ?g. }
- W4362637048 abstract "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 (Lcp1) knockout mice to suppress subchondral osteoclasts in a mice OA model with anterior cruciate ligament transection (ACLT), and Lcp1-/- 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-1α) in chondrocytes and led to cartilage degeneration. Lcp1 knockout impeded angiogenesis, which maintained hypoxia environment in joints and delayed the OA progression. Stabilization of HIF-1α delayed cartilage degeneration, and knockdown of Hif1a abolished the protective effects of Lcp1 knockout. Last, we showed that Oroxylin A, an Lcp1-encoded protein l-plastin (LPL) inhibitor, could alleviate OA progression. In conclusion, maintaining hypoxic environment is an attractive strategy for OA treatment." @default.
- W4362637048 created "2023-04-07" @default.
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- W4362637048 date "2023-04-05" @default.
- W4362637048 modified "2023-10-06" @default.
- W4362637048 title "Maintaining hypoxia environment of subchondral bone alleviates osteoarthritis progression" @default.
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- W4362637048 doi "https://doi.org/10.1126/sciadv.abo7868" @default.
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