MiR-637 Inhibits Osteogenic Differentiation of Human Intervertebral Disc Cartilage Endplate Stem Cells by Targeting WNT5A

Abstract

Background: Degenerative disk disease (DDD) remains the leading incentive of severe lumbago. DDD is mainly caused by degeneration of cartilage endplate (CEP). Cartilage endplate stem cells (CESCs) are essential in chondrogenesis and osteogenesis of CEP. This study investigated the mechanism of miR-637 inhibiting osteogenic differentiation of human CESC by regulating WNT5A. Methods: The degenerative CEP (N = 10) and non-degenerative CEP (N = 6) were obtained from patients undergoing disk fusion surgery. CESCs were examined for surface stem cell markers, alkaline phosphatase (ALP) levels, osteogenic differentiation, osteogenic genes (Runx2, COL1), and chondrogenic gene (COL2). The miR-637 expression in CESCs was detected. The targeting relationship of miR-637 and WNT5A was confirmed. After miR-637 overexpression/WNT5A down-regulation, the action of miR-637/WNT5A on osteogenic differentiation of CESCs was evaluated. After simultaneous overexpression of miR-637/WNT5A, the effect of miR-637 on osteogenic differentiation of CESCs was assessed. Results: miR-637 was down-expressed in degenerative CESCs (D-CESCs), and miR-637 overexpression inhibited the osteogenic differentiation of D-CESCs, while inhibition of miR-637 promoted the osteogenic differentiation ability of D-CESCs. miR-637 targeted WNT5A and down-regulation of WNT5A inhibited the osteogenic differentiation of D-CESCs. Up-regulated WNT5A partially annulled the inhibitory action of miR-637 overexpression on osteogenic differentiation of D-CESCs. Conclusion: miR-637 inhibited osteogenic differentiation of D-CESCs via targeting WNT5A.