RESUMO
OBJECTIVES: Osteoclast differentiation and bone resorption are considered a potential therapeutic target to the treatment of erosive bone diseases, including osteoporosis and rheumatoid arthritis. Poria cocos Wolf (PCW), commonly used herbal medicine, has previously been reported to induce anti-inflammatory effect and anti-cancer effect, and to modulate immunologic responses. However, the effects of PCW on osteoclasts, and its detailed mechanisms are not proven. Therefore, we examined the inhibitory mechanism of PCW on osteoclast differentiation and bone resorption. MATERIALS AND METHODS: To analyze the effects of PCW on osteoclast differentiation, we examined osteoclast differentiation in bone marrow macrophages (BMMs) treated with or without of PCW by TRAP staining. The expression of c-Fos, NFATc1, TRAP and OSCAR mRNA was determined by RT-PCR and the protein levels of c-Fos, NFATc1, p38, ERK, JNK, Akt and IkappaB were assessed by western blot. Also, we evaluated the effect of PCW on bone resorption using hydroxyapatite plate. RESULTS: PCW significantly inhibited RANKL-mediated osteoclast differentiation without any evidence of cytotoxicity. We founded that PCW strongly inhibited RANKL-induced osteoclast formation when added during the early stage of cultures, suggesting that PCW acts on osteoclast precursors to inhibit RANKL/RANK signaling. Among the RANK signaling pathways, PCW inhibited the phosphorylation of p38 and JNK, also inhibited RANKL-induced expression of c-Fos, NFATc1, TRAP and OSCAR. In addition, PCW suppressed the bone resorption of mature osteoclasts. CONCLUSIONS: These findings suggest that PCW may be a potential novel drug for bone disorders by targeting the differentiation of osteoclasts as well as their functions.
