Effect of Chordin-Like 1 on Differentiation of Bone Marrow Mesenchymal Stem Cells Through Wnt5/TGF-β Signaling Pathway

Chordin-like 1 (CHRDL1) functions in multiple tissues and organs. However, whether CHRDL1 affects bone marrow mesenchymal stem cells (BMSCs) differentiation remain unclear. Rat BMSCs were isolated and divided into control group, CHRDL1 group and CHRDL1 siRNA group followed by analysis of CHRDL1 level by real time PCR and ELISA, cell proliferation by MTT assay, Caspase 3 activity, ALP activity, expression of o Runx2, OC and PPAR gamma 2 by Real time PCR, TGF-beta secretion by ELIS, and Wnt5 protein expression by Western blot. CHRDL1 expression was significantly increased in CHRDL1 group, along with significantly promoted cell proliferation, decreased Caspase 3 activity, increased ALP activity and expression of Runx2 and OC, decreased PPAR gamma 2 expression, increased TGF-beta secretion and Wnt5 expression compared to control group (P < 0.05). However, CHRDL1 siRNA transfection significantly decreased CHRDL1 expression, inhibited cell proliferation, increased Caspase 3 activity, decreased ALP activity and Runx2 and OC expression, increased PPAR gamma 2 expression, decreased TGF-beta secretion and Wnt5 expression. (P < 0.05). Down-regulation of CHRDL1 expression in BMSCs promotes Wnt5/TGF-beta signaling transduction, which in turn increases BMSCs proliferation and osteogenic differentiation. Up-regulation of CHRDL1 expression in BMSCs inhibited the activation of Wnt5/TGF-beta signaling pathway, promoted BMSCs apoptosis, and inhibited BMSCs proliferation and osteogenic differentiation.