Maintaining hypoxia environment of subchondral bone alleviates osteoarthritis progression.
Sci Adv
; 9(14): eabo7868, 2023 04 05.
Article
en En
| MEDLINE
| ID: mdl-37018403
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Osteoartritis
/
Cartílago Articular
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Sci Adv
Año:
2023
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Estados Unidos