Jingui Shenqi Pills Prevents and Treats Postmenopausal Osteoporosis via Regulating the BMP/Smad Signaling Pathway

Abstract Background: Jingui Shenqi （JGSQ for short）pills is a traditional Chinese medicine formula, which has the functions of warming and tonifying kidney-yang, generating essence and filling marrow, warming tendons and veins and bones, and improving bone mineral density. The aim of this study was to investigate the effect and mechanism of JGSQ pills in preventing and treating postmenopausal osteoporosis.Methods : Twelve-week-old SPF female SD rats (n=48) were used in this study. Following the ovariectomy operation (n=40), the rats were randomly divided into the model group, (high, medium, and low dose groups) treated with Jingui Shenqi pills and estradiol group. Recorded the weight gain of rats and calculated the uterine coefficient; To detect the expression of serum calcium, phosphorus, ALP and OPG; HE staining was used to detect the pathological changes of femur; In all the groups, Micro-CT was used for detection of bone mineral density and bone microstructure; and gene expression of BMP-2, Smad1, and Runx2 in rat bone tissue was determined by RT-PCR and Western Blot methods.Results: Compared with the sham operation group, rats in the model group had the highest increase in body weight and the lowest uterine coefficient. Each of the treatment groups had a modest increase in weight gain. Micro-CT and HE staining showed a decrease in bone mineral density in the model group with shorter, thinner, broken, and osteoporotic trabeculae of the femur. The bone mineral density in Jingui Shenqi pills treatment groups had a significant increase with an improved bone microstructure and intact bone trabecular as compared to the model group. Serum ALP in the model group was significantly higher than in the sham operation group but the serum calcium, phosphorus and OPG was significantly lower. The Jingui Shenqi pills treatment groups and the estradiol treated group had lower serum ALP and increased serum calcium, phosphorus and OPG.There was decreased gene expression of BMP-2, Smad1, and Runx2 in the bone tissue of the model group compared to the sham operation group. BMP-2, Smad1, and Runx2 gene expression in Jingui Shenqi pills treated group and estradiol treated group was significantly higher than that of the model group.Conclusion: Jingui Shenqi pills improve the microstructure of bone tissue and increase bone mineral density thus resolving osteoporosis. This is achieved by regulating BMP/Smad signaling pathway and increasing the expression of osteogenic factors BMP-2, Smad1, and Runx2.