Geraniin promotes osteoblast proliferation and differentiation via the activation of Wnt/β-catenin pathway

Geraniin is an ellagitannin isolated from Phyllanthus amarus and has a wide range of bioactivities. Our previous study demonstrated that geraniin could alleviate osteoporosis by accelerating bone formation, but the mechanism remains unclear. This study aimed to elucidate the molecular mechanisms by which geraniin promotes osteoblast proliferation and differentiation in vitro. Primary rat bone marrow-derived mesenchymal stem cells were separated and divided into sham operated (Sham) group, Sham treated with geraniin (Sham + GE) group, ovariectomized (OVX) group, OVX treated with geraniin (OVX + GE) group, OVX treated with osteogenic medium (OVX + OM) group, OVX treated with Wnt inhibitor (OVX + WI) group, and OVX treated with Wnt inhibitor and geraniin (OVX + WI + GE) group. Following bilateral ovariectomy, the expression of beta-catenin, frizzled2, LRP6, TCF4, LEF1, c-myc, cyclin D1, Runx2 and osterix significantly reduced, while the expression of axin2 significantly increased (P < 0.05). Geraniin enhanced the expression of beta-catenin, frizzled2, LRP6, TCF4, LEF1, c-myc, cyclin D1, Runx2 and osterix, while inhibited the expression of axin2 (P < 0.05). Wnt inhibitor significantly weakened geraniin-induced Wnt/beta-catenin activation (P < 0.05). In conclusion, geraniin enhances the activation of Wnt/beta-catenin pathway, which may explain how it promotes osteoblast proliferation and differentiation.