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

Abstract

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.