Effects of gallotannin on osteoclastogenesis and the p38 MAP kinase pathway

Abstract

PurposeOsteoclasts are multinucleated giant cells that specialize in bone resorption and work together with bone-forming osteoblasts to maintain bone homeostasis. However, excessive osteoclast activation accounts for bone diseases, such as osteoporosis and periodontitis. In previous studies, natural small-molecule compounds have been shown to regulate osteoclastogenesis and osteoclast functions. Here we demonstrate that gallotannin, a hydrolyzable plant tannin, suppresses osteoclast differentiation. MethodsWe first used an ex vivo bone marrow culture system containing both osteoclast precursors and surrounding cells, thereby resembling physiological conditions, to evaluate the suppressive effect of gallotannin. We also used a RANKL-induced osteoclastogenesis assay containing only osteoclast precursors to confirm the suppressive effect of gallotannin in the absence of effects from other cells. ResultsThe suppressive effect of gallotannin was associated with the reduced RANKL-mediated induction of NFATc1, a critical transcription factor involved in osteoclast differentiation. We further confirmed that gallotannin reduced the p38 MAPK pathway activation, which is mediated by M-CSF and RANKL. This pathway suppression might underlie the suppression of NFATc1 production and subsequent reduction in osteoclast differentiation. ConclusionOur data indicate that the natural small-molecule compound gallotannin might be useful as a novel anti-bone resorptive agent.