Buqi-Tongluo Decoction Inhibits Osteoclastogenesis and Alleviates Bone Loss in Ovariectomized Rats by Attenuating NFATc1, MAPK, NF-κB Signaling

Background: Osteoporosis is the most common skeletal condition that is characterized by decreased bone mass and bone strength and increased fragility. Buqi-Tongluo (BQTL) decoction is a traditional Chinese medicine (TCM) prescription and its role in treating bone diseases such as osteoporosis has yet to be determined. Objective: Explore the mechanism of how Buqi-Tongluo (BQTL) decoction inhibits osteoclast differentiation in vitro and supplement it with in vivo experiments for validation. Methods: We utilized MTS assay to determine whether BQTL, at certain concentrations, has any proliferative or toxic effects on BMMs (Bone Marrow Macrophages), and combined it with TRAcP experiments to investigate the impact of BQTL on osteoclast differentiation. RT-PCR and Western blot were employed to assess the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were conducted to establish an osteoporosis model, further validating the reliability of the in vitro findings. Results: In this study, BQTL was found to suppress RANKL-induced osteoclastogenesis and osteoclast resorption activity in vitro dose-dependently without any observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, mainly through attenuating the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL’s inhibitory capability was also examined in vivo using an ovariectomized rat model, in which our results demonstrated that BQTL had strong protective effect against bone loss. Conclusion: BQTL may be an effective therapeutic TCM to treat postmenopausal osteoporosis and alleviate bone loss-induced estrogen deficiency and related diseases.