Interleukin-34 orchestrates bone formation through its binding to Bone Morphogenic Proteins

During growth, the contribution of IL34, a ligand of MCSFR, have not been established. The aim of this work was therefore to establish these implications using two models of IL34 invalidation generated in zebrafish and mouse. Significant growth delay and hypo-mineralization of skeletal elements were observed in both models, as well as craniofacial dysmorphoses in mice. With regard to bone cells, an unexpected increase in the number of osteoclasts and an accumulation of pre-osteoblasts were observed. In vitro analyses complemented by protein binding and molecular docking studies established that IL34 interacts directly with certain Bone Morphogenetic Proteins, modulating their various activities such as the stimulation of osteoblast differentiation. A new mechanism of action for IL34 has thus been characterized, opening up new therapeutic perspectives.