Myostatin induces subchondral bone destruction and cartilage matrix degradation through upregulation of the Wnt/β-catenin pathway during patellofemoral osteoarthritis.

Abstract

The pathogenesis of patellofemoral osteoarthritis (PFOA) is not fully understood. The aim of this project was to investigate the role and mechanism of myostatin (MSTN) in PFOA pathogenesis. Fifteen New Zealand white rabbits were divided into the following three groups: the control group, the model group and the MSTN-induced group. After 6 weeks, histopathological studies and osteoclast staining observations were carried out. The expression of genes related to osteoclast differentiation-related pathways, cartilage degradation and extracellular matrix deposition was also assessed. In addition, we investigated how macrophage transfection with a β-catenin overexpression plasmid affects osteoblast differentiation and downstream protein levels of RANKL and Smad2. MMP-13 levels were also detected to assess the extent of cartilage degradation. MSTN-induced subchondral bone and cartilage destruction in the patellofemoral joint was observed during histopathological examination, and osteoclast proliferation was observed via TRAP staining. The expression levels of β-catenin, MMP-13, Smad2, and RANKL were significantly increased, and the level of collagen II was significantly decreased in the samples. The expression levels of Smad2, RANKL and MMP-13 were significantly increased after the overexpression of β-catenin in macrophages. MSTN contributes to the progression of PFOA, induces subchondral bone destruction and cartilage matrix degradation in the patellofemoral joint, and promotes osteoclast differentiation through upregulation of the Wnt/β-catenin pathway.