Origin and role of inflammatory osteoclasts, novel therapeutic targets in rheumatic diseases – ORIOS
Chronic inflammatory diseases are frequently associated to rheumatic manifestation and bone destruction by osteoclasts (OCLs). This destruction is due to the activated immune cells that infiltrate the bone marrow where they produce cytokines that stimulate OCL differentiation, even when the inflammatory site is not the bone, as in Crohn's disease (IBD). Thus, inflammatory bone damages rely on complex interactions between activated immune cells and OCLs progenitors, on the traffic of these cells from the site of inflammation to the bone marrow, and on the modifications they induce in the bone marrow environment that affect its integrity. However, the mechanisms involved in this link between inflammation and osteopenia are still poorly understood. Recent data reveal that OCLs are not only bone-resorbing cells but also direct players involved in controlling inflammatory responses. Depending on their context (normal or pathological), they induce immune suppressive or inflammatory responses. This is a very novel picture of their contribution to rheumatic diseases, pointing inflammatory OCLs (i-OCLs) as very interesting therapeutic targets. Our aims are to determine the origins and markers of i-OCLs, to understand their contribution to inflammation and to develop approaches for specific targeting of i-OCLs to limit inflammatory bone destruction. We will combine analyses in murine models of inflammatory bone destruction (arthritis, IBD) and studies in patients. The results will open new clues for therapeutic approaches, diagnosis and outcome markers for inflammatory bone destruction, and new insight for a forsaken aspect of OCL biology. They may also impact other pathologies related to bone destruction, such as osteoporosis or osteolytic tumor.
Madame Claudine Blin-Wakkach (Laboratoire de physiomdecine moléculaire, équipe "ostéoimmunologie, niches et inflammation")
The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.
Inserm U1173 - 2I Infection et Inflammation, Inserm U1173
CNRS DR20_LP2M Laboratoire de physiomdecine moléculaire, équipe "ostéoimmunologie, niches et inflammation"
INSERM u1183 Cellules souches, plasticité cellulaire, Médecine Régénératrice et immunothérapies
Help of the ANR 624,813 euros
Beginning and duration of the scientific project: December 2016 - 48 Months