Leucine Attenuates Osteoarthritis via mTORC1/LXRα-Mediated Macrophage Reprogramming and Rspo2/β-Catenin Axis Suppression.

ABSTRACT: ObjectiveThis study investigates the molecular mechanism by which leucine (Leu) ameliorates collagenase-induced osteoarthritis (CIOA) through macrophage polarization regulation.MethodsA CIOA mouse model was established and evaluated by micro-computed tomography (micro-CT) and histopathological analysis. Leu intervention was administered, and its therapeutic effects on cartilage degeneration and osteophyte formation were assessed. Integrated multi-omics analyses and mechanistic assays were performed to explore the role of the mTORC1/LXRα pathway in synovial macrophage reprogramming and its regulation of the Rspo2/β-catenin axis in chondroprogenitors. Functional validation was conducted using the LXRα inhibitor GSK2033.ResultsLeu intervention demonstrated significant therapeutic effects, red

SUBMITTER: Zheng K 

PROVIDER: S-EPMC12597797 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature