Overexpression of Heme Oxygenase-1 Promotes Osteoblast Differentiation of Osteoporosis Rat Bone Marrow Stromal Cells in Bone Morphogenetic Protein-Dependent Manner

Abstract

BMSCs play a role in osteoporosis (OP) and their differentiation can lead to OP progression. Heme oxygenase-1 (HO-1) involves in many diseases, but the effect of HO-1 on osteoblast differentiation of BMSCs in OP rats remains unclear. SD rats were divided into control group and OP group. Rats BMSCs in OP group were cultured in vitro, HO-1 expression was up-regulated by HO-1 agonist hemin, and BMPR inhibitor LDN-19318 was added followed by analysis of HO-1 expression by real time PCR and ELISA, cell proliferation by MTT assay, apoptosis by Caspase 3 activity, BMP-2 expression by Western blot, ALP activity, expression of Runx2 and OC by real time PCR. In OP group, HO-1 expression was significantly decreased, cell proliferation was inhibited, Caspase 3 activity was increased along with decreased ALP activity and expression of Runx2, OC and BMP-2 compared to control (P < 0.05). Up-regulation of HO-1 expression significantly promoted cell proliferation, reduced Caspase 3 activity, increased ALP activity, and expression of Runx2, OC and BMP-2 (P < 0.05). However, inhibition of HO-1 significantly promoted bone differentiation after the addition of BMPR inhibitor LDN-193189 (P < 0.05). HO-1 expression is decreased in BMSCs of OP group rats. Up-regulation of HO-1 promoted BMSCs proliferation in OP rats in BMP-dependent manner, inhibited apoptosis, and promoted osteoblast differentiation.