Fu Fang Sheng Mai capsules inhibit osteoclast formation and improve osteoporosis caused by oophorectomy in mice.

BACKGROUND

Postmenopausal osteoporosis (PMOP) is a critical bone metabolic disorder marked by progressive bone loss and compromised bone microstructure. Empirical clinical observations suggest that Fu Fang Sheng Mai Capsules (FFSM) can effectively alleviate symptoms of osteoporosis; however, their underlying molecular mechanisms remain insufficiently defined. The present study was designed to investigate the regulatory effects of FFSM on osteoclast differentiation and to evaluate its therapeutic potential in PMOP.

METHODS

Bone marrow-derived macrophages (BMMs) were isolated and induced to differentiate into osteoclasts in vitro. The impact of FFSM on osteoclastogenesis was assessed by tartrate-resistant acid phosphatase (TRAP) staining and F-ACTIN ring fluorescence staining. Subsequently, quantitative real-time PCR (qRT-PCR) and Western blot analyses were performed to evaluate the expression of osteoclast-specific genes, with further mechanistic investigations. For in vivo validation, a bilateral ovariectomy model was established in C57BL/6 mice, and bone quality was examined using micro-CT and histological analysis.

RESULTS AND

CONCLUSION

FFSM significantly suppressed osteoclast formation and F-ACTIN ring assembly, with notable downregulation of osteoclast differentiation markers NFATc1 and Acp5 observed at days 3-5. Mechanistically, FFSM reduced intracellular ROS levels within osteoclasts, and specifically inhibited the phosphorylation of key signaling proteins, p-P65 in the NF-κB pathway and p-JNK in the MAPK pathway, thus interfering with pathways critical for osteoclastogenesis. Consistent with in vitro findings, in vivo studies revealed that FFSM reduced osteoclastogenesis and effectively rescued bone mass loss.