The molecular mechanisms linking immune cell signaling to osteoclastogenesis remain incompletely defined. Here, we identify an Annexin A1 (AnxA1)-Dectin-1 axis as a key driver of osteoclast differentiation. Dectin-1 (CLEC7A), a myeloid C-type lectin receptor best known for β-glucan recognition, is shown to bind the endogenous ligand AnxA1 on pre-osteoclasts, thereby promoting their maturation. In Dectin-1 deficient mice, reduced osteoclast numbers resulted in increased bone volume, whereas β-glucan-induced Dectin-1 activation enhanced osteoclastogenesis. Within the bone marrow niche, AnxA1 was abundantly expressed on B220+ B cells, and γ-irradiation markedly increased its surface translocation both in vitro and in vivo. γ-irradiated B220+ B cells exhibited strong Dectin-1 binding capacity and robustly stimulated osteoclast differentiation in a Dectin-1-dependent manner. These findings establish the AnxA1-Dectin-1 interaction as a critical immune-skeletal communication pathway, revealing a mechanism by which radiation exposed immune cells can accelerate bone resorption. Targeting this axis offers a potential strategy to mitigate radiation-induced bone degradation and preserve skeletal homeostasis.
Guliyeva et al. (Wed,) studied this question.