Lef1 ablation alleviates cartilage mineralization following posttraumatic osteoarthritis induction

Abstract

Significance Cartilage mineralization is imperative in various processes such as skeletal growth and fracture repair. However, this process may also be pathological, as in the case of the degenerative joint disease, osteoarthritis (OA). Using a posttraumatic OA model (PTOA), we find that cartilage-specific Sirt1 genetic nulls caused severe synovitis and mineralization of the lateral joint compartment, due to augmented Lef1 gene expression. Conversely, cartilage-specific Lef1 nulls exhibited impaired synovitis and mineralization of the lateral joint, accompanied by a reduction of local pain. Consistently, transcriptomic profiles of Lef1 -ablated chondrocytes exhibited enhanced anabolism, yet impaired pathways related to calcification and inflammation. Accordingly, cartilage mineralization of the lateral joint compartment relies on amplified inflammatory pathways, contributing to articular damage following PTOA.