| First Author | Zhang H | Year | 2023 |
| Journal | Sci Adv | Volume | 9 |
| Issue | 14 | Pages | eabo7868 |
| PubMed ID | 37018403 | Mgi Jnum | J:353271 |
| Mgi Id | MGI:7460797 | Doi | 10.1126/sciadv.abo7868 |
| Citation | Zhang H, et al. (2023) Maintaining hypoxia environment of subchondral bone alleviates osteoarthritis progression. Sci Adv 9(14):eabo7868 |
| abstractText | 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-1alpha) 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-1alpha 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. |
