Physcion Alleviates Osteoporotic Bone Loss by Inhibiting Osteoclast Formation and Promoting Osteoblast Differentiation.

BACKGROUND

Osteoporosis is a prevalent bone disorder resulting from imbalanced bone remodeling, characterized by excessive bone resorption and insufficient bone formation. Physcion, a natural anthraquinone, exhibits diverse pharmacological activities; however, its effects on bone remodeling remain unclear.

OBJECTIVE

This study aimed to investigate the potential of physcion in mitigating osteoporotic bone loss by regulating the differentiation and activity of osteoclasts and osteoblasts.

METHODS

In vitro, the effects of physcion on osteoclastogenesis and osteoblast differentiation were assessed using bone marrow-derived monocytes (BMMs) and bone marrow mesenchymal stem cells (MSCs) treated with various non-cytotoxic doses (0, 0.1, 1, and 10 µM). Osteoclast formation and function were evaluated using tartrate-resistant acid phosphatase (TRAP) staining and bone resorption assays. Osteoblast differentiation was assessed by alkaline phosphatase (ALP) staining and activity measurement. Expression of key markers and activation of signaling pathways associated with osteoclasts and osteoblasts were analyzed by Western blotting and quantitative real-time PCR (qPCR). In vivo, ovariectomy (OVX)-induced osteoporotic mice were treated with physcion (5 mg/kg, twice weekly) for 8 weeks, and bone microarchitecture was analyzed using micro-CT.

RESULTS

Physcion dose-dependently inhibited receptor activator of nuclear factor κB ligand (RANKL)- induced osteoclast formation and bone resorption by suppressing the nuclear factor κB (NF-κB) and p38 MAPK pathways and downregulating osteoclast-specific genes (e.g., NFATc1 and CTSK). Simultaneously, it promoted osteoblast differentiation and increased the expression of osteogenic markers (RUNX2, OSX, and COL1), associated with activation of SMAD1/5/9 and ERK1/2 signaling pathways. In vivo administration of physcion significantly attenuated OVX-induced bone loss.

DISCUSSION: These findings indicate that physcion holds promise as a natural agent for preventing bone loss.

CONCLUSION

Physcion exhibits dual osteoprotective effects by inhibiting osteoclast differentiation and enhancing osteoblast formation, suggesting its potential as a therapeutic agent for osteoporosis.