MMP-2 silencing reduces the osteogenic transformation of fibroblasts by inhibiting the activation of the BMP/Smad pathway in ankylosing spondylitis

摘要

Ankylosing spondylitis (AS) is a common type of rheumatoid disease, which has recently been demonstrated to be associated with the expression of matrix metalloproteinase (MMP)-2. The aim of the present study was to investigate whether MMP-2 interference reduced the osteogenic differentiation of fibroblasts and to explore the mechanism involved in the differentiation. Fibroblasts from patients with AS were divided into control, mock and small interfering (si) RNA-MMP-2 groups. Cell viability was assessed using the MTT assay. mRNA and protein expression levels of MMP-2, core-binding factor a1 (Cbfa-1) and bone morphogenetic proteins/Smad-signalling molecules (BMP/Smad) were measured using reverse transcription-quantitative polymerase chain reaction and western blotting. The results indicated that cell viability and fibroblast morphology did not differ significantly between healthy volunteers and patients with AS. However, MMP-2 expression levels in AS fibroblasts were substantially higher. MMP-2 gene silencing markedly downregulated the expression of MMP-2 and Cbfa-1, and inhibitied the activation of the BMP/Smad signalling pathway consequent to the reduction in levels of BMP-2, Smad1, Smad4 and Smad1/5/8. The results showed that MMP-2 gene silencing may reduce the osteogenesis of fibroblasts in AS by inhibiting the activation of the BMP/Smad signalling pathway.