miR-195 contributes to human osteoarthritis via targeting PTHrP.

ABSTRACT

The dysregulated expression of the osteoarthritis (OA)-related genes in cartilage, such as matrix metalloproteinase 13 (MMP-13) and type X collagen (Col X), facilitates the onset and progression of OA. Reduced parathyroid hormone-related protein (PTHrP) may also accelerate this progression. Furthermore, miRNAs, endogenous regulators of mRNAs, are thought to play key roles in the pathogenesis of OA. In this study, we found that miR-195 levels were significantly upregulated in OA tissue, while PTHrP mRNA/protein expression was substantially downregulated, and there was a negative correlation between miR-195 and PTHrP. Upregulated miR-195 strongly inhibited Aggrecan, type II collagen (Col II) mRNA/protein expression, while it enhanced the expression of MMP-13 and Col X at mRNA/protein level; conversely, downregulated miR-195 significantly increased Col II mRNA/protein expression, while it decreased the expression of MMP-13 and Col X mRNA/protein. Moreover, our study demonstrated that PTHrP is a novel target of miR-195 using dual luciferase reporter assay. Finally, miR-195-mediated changes of Col II and OA-related genes were substantially attenuated by siRNAPTHrP treatment. These results suggested that miR-195 is involved in the pathogenesis of OA via PTHrP.