Ellagic acid inhibits RANKL-induced osteoclast differentiation by suppressing the p38 MAP kinase pathway

다국어 초록 (Multilingual Abstract)

Bone undergoes continuous remodeling by acoupled action between osteoblasts and osteoclasts. Duringosteoporosis, osteoclast activity is often elevatedleading to increased bone destruction. Hence, osteoclastsare deemed as potential therapeutic targets to alleviatebone loss. Ellagic acid (EA) is a polyphenol reported topossess anticancer, antioxidant and anti-inflammatoryproperties. However, its effects on osteoclast formationand function have not yet been examined. Here, weexplored the effects of EA on RANKL-induced osteoclastdifferentiation in RAW264.7 murine macrophages(in vitro) and human CD14?monocytes (ex vivo). EAdose-dependently attenuated RANKL-induced TRAP?osteoclast formation in osteoclast progenitors with maximalinhibition seen at 1 lM concentration without cytotoxicity.
Moreover, owing to perturbed osteoclastogenesis,EA disrupted actin ring formation and bone resorptivefunction of osteoclasts. Analysis of the underlyingmolecular mechanisms revealed that EA suppressed thephosphorylation and activation of the p38 MAP kinasepathway which subsequently impaired the RANKL-induceddifferentiation of osteoclast progenitors. Takentogether, these novel results indicate that EA alleviatesosteoclastogenesis by suppressing the p38 signaling pathwaydownstream of RANKL and exerts inhibitory effectson bone resorption and actin ring formation.

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