Maintaining hypoxia environment of subchondral bone alleviates osteoarthritis progression

• DOI: 10.1126/sciadv.abo7868
• Publication Date: 2023-04-05T17:58:37Z
• Authors: Hao Zhang; Lipeng Wang; Jin Cui; Sicheng Wang; Yafei Han; Hongda Shao; Cheng Wang; Yan Hu; Xiaoqun Li; Qirong Zhou; Jiawei Guo; Xinchen Zhuang; Shihao Sheng; Tao Zhang; Dongyang Zhou; Jiao Chen; Fuxiao Wang; Qianmin Gao; Yingying Jing; Xiao Chen; Jiacan Su
• Keywords: Knockout mouse; Hypoxia; Degeneration (medical)

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 suppress osteoclasts in a OA model with anterior cruciate ligament transection (ACLT), Lcp1-/- showed decreased retarded degeneration. For mechanisms, activated induced type-H vessels elevated oxygen concentration, which ubiquitylated hypoxia-inducible factor alpha subunit (HIF-1α) chondrocytes led Lcp1 impeded angiogenesis, maintained hypoxia environment joints delayed progression. Stabilization of HIF-1α degeneration, knockdown Hif1a abolished protective effects knockout. Last, we that Oroxylin A, an Lcp1-encoded l-plastin (LPL) inhibitor, could alleviate In conclusion, maintaining hypoxic attractive strategy for treatment.