Interleukin-3 as a Potential Bone Anabolic Agent in treating Postmenopausal Osteoporosis

Postmenopausal osteoporosis (PMO), a silent disorder caused due to estrogen deficiency, is characterized by loss of bone mass and low bone mineral density. Despite advancements in treatment, current medications often fail to fully restore bone integrity and prevent fragility fractures in the osteoporotic individuals. Thus, there is a high demand of novel therapeutic modalities in dealing with osteoporosis. Interleukin-3 (IL-3), a cytokine secreted by activated T cells, emerges as a promising therapeutic candidate. The dual role of IL-3 in inhibiting osteoclast differentiation and promoting osteoblast differentiation, offers protection against bone and joint degeneration in arthritic mice. However, its role in osteoporosis is not yet delineated. Therefore, our investigation focuses on elucidating the role of IL-3 in PMO, employing both prophylactic and therapeutic strategies in ovariectomized mice, mimicking human PMO. In our study, at the onset of osteoporosis, IL-3 treatment effectively preserved trabecular bone architecture and enhanced bone mineral density in OVX mice, particularly notable in therapeutic interventions where fully developed osteoporosis was addressed. Notably, in preventive measures, IL-3 inhibited osteoclast differentiation, thereby suppressing bone resorption, while in therapeutic approaches, it enhanced osteoblast differentiation, promoting bone formation. Irrespective of gender specific, microCT analysis of IL-3-/- (KO) mice showed reduced trabecular bone development compared to its respective wild type (WT) mice, highlighting essential role of IL-3 in skeletal integrity. Moreover, IL-3 increased Treg cells population while inhibiting B cell lymphopoiesis in ovariectomized mice with no adverse effects on hematopoiesis or vital organs. In conclusion, our findings collectively underscore the potential of IL-3 as a novel therapy for PMO, offering insights into its mechanisms of action and clinical applications. One Sentence SummaryIL-3 has a dual action on bone: anti-osteoclastic and pro-osteoblastic in OVX mice, thus can be a novel therapeutic drug in treating postmenopausal osteoporosis.