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

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.