Abstract
Astragalin (AG) is a biologically active flavonoid compound that can be extracted from a number of medicinal plants. However, the effects of AG on osteoblastic differentiation in mouse MC3T3-E1 cells and on bone formation in vivo have not been studied fully. In this study, we found that the activities of alkaline phosphatase (ALP) and mineralized nodules in MC3T3-E1 cells were both significantly increased after treatment with AG (5, 10, and 20 μM). Meanwhile, the mRNA and protein levels of osteoblastic marker genes in MC3T3-E1 cells after AG treatment were markedly increased compared with a control group. In addition, the levels of BMP-2, p-Smad1/5/9, and Runx2 were significantly elevated in AG-treated MC3T3-E1 cells. Moreover, we found that the protein levels of Erk1/2, p-Erk1/2, p38, p-p38, and p-JNK were also significantly increased in AG-treated MC3T3-E1 cells compared to those in the control group. Finally, in vivo experiments demonstrated that AG significantly promoted bone formation in an ovariectomized (OVX)-induced osteoporotic mouse model. This was evidenced by significant increases in the values of osteoblast-related parameters (BFR/BS, MAR, Ob.S/BS, and Ob.N/B.Pm) and bone histomorphometric parameters (BMD, BV/TV, Tb.Th, and Tb.N.) in OVX mice after AG treatment (5, 10, and 20 mg/kg). Collectively, these results demonstrated that AG may promote osteoblastic differentiation in MC3T3-E1 cells via the activation of the BMP and MAPK pathways and promote bone formation in vivo. These novel findings indicated that AG may be a useful bone anabolic agent for the prevention and treatment of osteoporosis.
Highlights
Osteoporosis is a systemic skeletal disease characterized by global damage to bone mass and an enhanced risk of bone fractures [1]
Astragalin (AG), called kaempferol-3-O-glucoside, is a flavonoid compound extracted from various traditional herbs and medicinal plants [11]
Our results demonstrated that AG significantly elevated alkaline phosphatase (ALP) activity in a concentration-dependent manner (Figure 1B)
Summary
Osteoporosis is a systemic skeletal disease characterized by global damage to bone mass and an enhanced risk of bone fractures [1]. It has been reported that one of the leading causes of increased health care costs in the United States is osteoporosis [3]. Astragalin Promotes Osteoblastic Differentiation and treatment of osteoporosis are urgent medical questions that needs to be answered. The maintenance of bone homeostasis requires coordinated work by both boneforming osteoblasts and bone-resorbing osteoclasts [5]. Osteoporosis occurs as a result of decreased bone formation induced by osteoblasts and increased bone resorption induced by osteoclasts. Recent studies have suggested that stimulation of osteoblast differentiation may prove to be an efficacious treatment strategy for the prevention and treatment of osteoporosis [6]
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