Compromised anti-osteoclastogenic and immunomodulatory functions of regulatory B cells (Bregs) aggravate inflammatory bone loss in post-menopausal osteoporosis

Abstract

Regulatory-B-cells (Bregs) modulate immune-homeostasis. Variations in the number and function of Bregs have been associated with various immune-related ailments, highlighting the importance of Bregs under inflammatory-conditions. Previously, we discovered the anti-osteoclastogenic-potential of Bregs. However, the crucial role of Bregs in the onset and progression of post-menopausal osteoporosis (PMO) has never been explored. Interestingly, our temporal-kinetic study demonstrated that Bregs have a compromised dynamics and functionality which further contributes to inception and the progression of the inflammatory bone loss condition in the PMO. Our ex-vivo findings further elucidate a significant reduction in the immunomodulatory and anti-osteoclastogenic functions of Bregs under the estrogen deficient post-menopausal osteoporotic conditions. The current study for the first time reports the crucial role of dysregulated-Bregs (both functionally and numerically), in the development of PMO. Our findings thereby provide a novel concept for immuno-therapeutically targeting “Bregs”, for effective management and treatment of post-menopausal osteoporosis in the long run.