Troxerutin Prevents Ovariectomy-Induced Bone Loss By Regulating Bone Formation And Bone Resorption

Aims:Postmenopausal osteoporosis is a bone metabolism disease that is caused by an imbalance between bone-resorbing osteoclast and bone-forming osteoblast actions.Herein,we describe the role of troxerutin(TRX),a trihydroxyethylated derivative of rutin,in ovariectomy(OVX)-induced osteoporosis and its effects on the regulation of osteoclasts and osteoblasts.Methods:In vivo,OVX female mice were intraperitoneally injected with either saline,50 mg/kg TRX,or 150 mg/kg TRX for 6 weeks and then sacrificed for micro-computed tomography analyses,histological analyses,and biomechanical testing.In vitro,RAW264.7 cell-derived osteoclasts and MC3T3-E1 cell-derived osteoblasts were treated with different concentrations of TRX to examine the effect of TRX on osteoclastogenesis and bone resorption,as well as on osteogenesis and mineralization.Results:In this study,we demonstrated that TRX prevented cortical and trabecular bone loss in ovariectomized mice by reducing osteoclastogenesis and promoting osteogenesis in vivo.In vitro,TRX inhibited the formation and activity of RAW264.7-derived osteoclasts and the expression of nuclear factor of activated T-cells 1 and cathepsin K.Meanwhile,TRX improved the osteogenesis and mineralization of MC3T3-E1 by enhancing the expression of Runt-related transcription factor 2,Osterix,and collagen type 1 alpha 1.Conclusions:Our data demonstrated that TRX could versatilely prevent OVX-induced osteoporosis and be used in a novel treatment for postmenopausal osteoporosis.