Poly-γ-glutamic acid suppresses osteoclastogenesis in human osteoclast precursors and prevents joint damage in a collagen-induced murine arthritis model

Poly-gamma-glutamic acid (gamma-PGA), a natural polymer derived from Bacillus subtilis, shows anti-inflammatory activity. However, the effects of gamma-PGA on osteoclasts, which are important cells for joint destruction in inflammatory diseases such as rheumatoid arthritis (RA), have not yet been reported. In this study, we show that gamma-PGA markedly inhibits osteoclast differentiation in normal PBMC-derived osteoclast precursors and in synovial fluid macrophages of patients with RA. gamma-PGA also reduces RANK expression by down-regulating M-CSF receptors. Additionally, oral administration of gamma-PGA attenuated bone destruction in a collagen-induced arthritis (CIA) model, demonstrating decreases in inflammation, cartilage damage, and osteoclast formation in histological analyses. Taken together, these data suggest that gamma-PGA could be a good candidate for therapeutic prevention of joint destruction in RA.