Geraniin promotes osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) via activating β-catenin: a comparative study between BMSCs from normal and osteoporotic rats.

Abstract

Abnormal osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) has been correlated with the pathogenesis of osteoporosis. Geraniin, a polyphenolic compound isolated from Phyllanthus amarus, is effective in preventing osteoporosis, but the mechanisms of action of geraniin and the impact of osteoporotic condition on drug action are not known. In this study we compared the proliferation and osteoblastic differentiation potential of BMSCs from normal rats with that from osteoporotic rats, and examined the responses of both BMSCs to geraniin in parallel. BMSCs of rats subjected to ovariectomy or sham operation were isolated and treated with geraniin. Cell proliferation was measured by CCK-8 assay. Osteoblastic differentiation was quantified by Alizarin Red S staining and alkaline phosphatase assay. Nuclear translocation of β-catenin was monitored by immunofluorescent staining. Expression of β-catenin was determined by Western blot and quantitative real-time polymerase chain reaction. Results showed that the proliferation and osteoblast formation of osteoporotic BMSCs decreased in comparison to that of normal BMSCs. Geraniin enhanced proliferation and osteoblastic differentiation of both BMSCs, but the responses of osteoporotic BMSCs to geraniin were less than those of normal BMSCs. Expression and nuclear accumulation of β-catenin in osteoporotic BMSCs were found to be diminished. Geraniin increased nuclear translocation and expression of β-catenin in both BMSCs. This study associated the osteogenic effect of geraniin to activation of Wnt/β-catenin signaling, and provided rationale for pharmacological investigation of geraniin in osteoporosis prevention and treatment.