Regulatory B cells (Bregs) inhibit osteoclastogenesis and prevent bone loss in osteoporotic mice model

Increasing evidences in recent years have suggested that regulatory B cells (Bregs) are the crucial modulator in various inflammatory disease conditions. However, the role of Bregs in case of postmenopausal osteoporosis remains understudied. Also, no study till date have ever investigated the significance of IL-10 secreting Bregs in modulating osteoclastogenesis under in vitro conditions. In the present study, we for the first time examined the anti-osteoclastogenic potential of Bregs under in vitro conditions and we observed that Bregs suppressed RANKL mediated osteoclastogenesis in bone marrow cells in a dose dependent manner. We further elucidated the mechanism behind the suppression of osteoclasts differentiation by Bregs and our flow cytometric data analysis suggested that Bregs inhibits osteoclastogenesis via IL-10 production. To further confirm the bone health modulating potential of Bregs we employed post-menopausal osteoporotic mice model. Remarkably, our in vivo data suggested that the frequencies of CD19+IL-10+ and CD19+CD1dhiCD5+IL-10+ B10 Bregs were significantly reduced (p < 0.01) in case of osteoporotic mice model. Moreover, our serum cytokine data corroborates with our flow cytometric data with significant reduction of IL-10 levels in osteoporotic mice. Taken together, the present study for the first time unravels and establish the unexplored role of regulatory B cells in case of osteoporosis and provide new insight into the Bregs biology in the context of post-menopausal osteoporosis.