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Facult� de m�decine et des sciences de la sant�

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OSTEOCLAST APOPTOSIS

The bone resorption process is involved in many clinical situations relevant for rheumatologists, such as focal bone destruction or erosion in rheumatoid arthritis, diffuse bone loss encountered in osteoporosis, focal increased in bone remodeling in Paget’s disease of bone, or osteolysis associated with malignant conditions.

The survival and apoptosis (programmed cell death) of bone cells are both of major importance in bone remodeling, and in diseases with hyperresorption, which can lead to crucial shifts in bone resorption. Osteoclast life span is the keystone to bone remodeling, and this process could offer a useful target in the treatment of skeletal disorders.We study the mechanisms involved in human osteoclast apoptosis, and its regulation in physiology as well as in bone disorders.

ROLE OF p62 IN OSTEOCLASTS AND IN PAGET'S DISEASE OF BONE

Paget's disease of bone is a common disorder of the elderly, and is characterized by excessive resorption and formation of bone, by phenotypically abnormal osteoclasts with numerous nuclei, and by increased survival. Mutations in the gene encoding p62 have been shown to be involved in the pathogenesis of Paget's disease of bone; however, its relationship to the Paget’s phenotype is still unclear. We thus investigate the effects of p62 mutations in the osteoclast activity and survival, as well as the osteoclast signaling.

BIOMATERIALS AND OSTEOCLASTIC BONE RESORPTION

The self-healing capacity of bone is widely used for the repair of small fractures but bone grafts are needed to provide support and enhance biological repair when a skeletal defect exceeds a critical size. Bone substitutes coupled with growth factor-derived peptides could be used, but their physical characteristics and the responses of bone cells to those materials have to be determined. Osteoclast bone resorption starts with matrix recognition and osteoclast attachment. Studying interactions between these cells and the peptides grafted-copolymers is thus of major importance in the evaluation of biomaterials as bone substitutes. This work will be done in collaboration with experts in engeneering (N. Faucheux, F. Gitzhofer, G. Baroud), molecular biologist (Dr Grenier), and orthopaedic surgeon (Dr Cabana).