Group 1: Origin, immune function and therapeutic targeting of inflammatory osteoclasts (C. Blin)

Equipe 1-groupe 1Bone is a tissue in perpetual renewal under the action of two cell types, the osteoblasts that make the bone matrix and the osteoclasts that resorb it. Bone formation and bone resorption are in balance, but during pathologies such as osteoporosis or chronic inflammatory diseases (rheumatoid arthritis, Crohn's disease, etc.) this balance is broken and bone resorption becomes more important than its formation, leading bone destruction and decreased bone mass.

This destruction has long been associated with an increase in the number of osteoclasts. But our recent work has shown that osteoclasts generated in pathological conditions are not only more numerous, but that they are also different from those present in normal condition. We have also demonstrated that, as the other cells of the monocytic lineage (from which they are derived), osteoclasts have a real immune function that has been neglected until now. Depending on their origin and their environment, they modulate inflammatory reactions to either immune tolerance or inflammation. They are also involved in the formation of niches for hematopoietic stem and progenitor cells.

Our current work aims to characterize inflammatory and non-inflammatory osteoclasts and to better understand their immune function. We seek to characterize the origin of these subpopulations of osteoclasts and the conditions that control their differentiation. We are also looking for specific markers to identify inflammatory and non-inflammatory osteoclasts and more broadly the functional pathways in which they are involved. Finally, thanks to these markers, we are evaluating new therapeutic approaches for bone destruction that specifically target inflammatory osteoclasts in order to preserve basic bone remodeling by physiological osteoclasts.