Resveratrol facilitates bone marrow mesenchymal stem cells (BMSCs) differentiation to prevent osteoporosis via restraining of secreted frizzled-related protein 1 expression

Abstract

Secreted frizzled-related protein 1 (SFRP1) is associated with cell differentiation, and its expression can be modulated by resveratrol. However, their impacts on bone marrow mesenchymal stem cells (BMSCs)-induced osteogenesis and ovariectomy-triggered bone loss remain unclear. Therefore, we in this study aimed to dissect the regulation of resveratrol on SFRP1, along with its sequential effects on differentiation and osteoporosis prevention of BMSCs. The SFRP1 expression in the ovariectomized (OVX) mice-originated bone tissues, BMSCs and bone marrow-derived macrophages (BMMs), during their differentiation towards osteoblasts and chondrocytes, was quantified by qRT-PCR and Western-blot. SFRP1-siRNA was applied for studying its influence on osteogenesis of BMSCs. Additionally, we evaluated the impacts of resveratrol on OVX mice and SFRP1 expression. SFRP1 was significantly up-regulated in the OVX mice-derived bone tissues and BMSCs, but gradually decreased during osteogenesis. Its expression was not significantly changed in BMSCs during their differentiation towards osteoclasts or in BMMs. The knockout of SFRP1 significantly improved mineralization potentiality, alkaline phosphatase activity and expression of several osteoblast-specific genes. Moreover, the bone loss was ameliorated in OVX mice treated with resveratrol, whose therapeutic effects were achieved by facilitating the expression of osteogenesis-associated genes while suppressing the SFRP1 expression. We also observed that the SFRP1 exerted a negative effect on osteogenesis of BMSCs and estrogen deficiency-induced osteoporosis, enabling itself to be an indicator of osteogenesis and also a molecular target for PMOP treatment. Resveratrol is a suppressor of SFRP1that can be applied as an active ingredient for treating PMOP.