2,5-Dihydroxyacetophenone attenuates RANKL-mediated osteoclastogenesis by affecting the NFATc1 signaling pathway in vitro.

[Display omitted] Excessive bone resorption activity of osteoclasts is a common characteristic of osteolytic conditions such as osteoporosis and inflammatory bone diseases. Natural compounds with antiosteoclastogenic function seem to be beneficial for the treatment of osteolytic diseases. In this study, we evaluated the effects of 2,5-dihydroxyacetophenone (DHAP), a phenolic compound in Ganoderma bambusicola, on osteoclastogenesis induced in vitro by the receptor activator of nuclear factor-κB ligand (RANKL). DHAP inhibited the differentiation, actin ring formation, and bone resorption activity of osteoclasts. In particular, DHAP inhibited the transcriptional activity of nuclear factor of activated T -cells cytoplasmic 1 (NFATc1) during osteoclastogenesis. This inhibition resulted in reduced expression levels of cathepsin k (Ctsk), tartrate-resistant acid phosphatase (Trap), and NFATc1 (Nfatc1), thereby reducing the differentiation of osteoclasts. However, DHAP did not affect reactive oxygen species production or activator protein 1 (AP-1) and nuclear factor kappa B (NF-κB) signaling. Our findings suggest that DHAP inhibits RANKL-induced osteoclastogenesis by inhibiting the NFATc1 signaling pathway. [ABSTRACT FROM AUTHOR]