Yishen Gushu Formula Attenuates Ovariectomy-Induced Bone Loss by Regulating the B-Cell Receptor Signaling Pathway in Rats.

Postmenopausal osteoporosis (PMOP) is a skeletal disorder induced by estrogen deficiency. Yishen Gushu formula (YSGSF) has been confirmed to exert positive regulatory effects on bone metabolism, while its underlying mechanism remains to be fully elucidated. In this study, a rat model of PMOP was established via ovariectomy. Following 12 weeks of intervention with YSGSF decoction, its mechanism of action was investigated using Micro-CT, HE staining, RNA sequencing, qRT-PCR, and Western blot. The results demonstrated that YSGSF significantly attenuated bone loss in PMOP rats. A total of 18 differentially expressed genes with expression trends reversed by YSGSF were screened out, and their functions were mainly enriched in B-cell differentiation, immunoglobulin complex, and B-cell receptor (BCR) signaling pathways. The expression levels of CD79A, CD79B, VPREB1, and VPREB3 were downregulated after YSGSF intervention. Collectively, YSGSF may alleviate bone microstructure impairment in PMOP rats by downregulating key genes in the BCR pathway and improving the skeletal immune microenvironment.