Research Lab (UPMC-INSERM UMR-S938)

Welcome!

Our team associates physiologists, cell biologists, biochemists, and clinicians devoted to the physiological and biological understanding of osteoarthritis, particularly by exploring the role of metabolism, inflammation, mechanical stress and bone/cartilage communication in this disease.

Research brief

 A few years ago, we started to look at the role of tissue interactions in osteoarthritis (OA),a disease initially considered as cartilage-driven. OA is a much more complex disease, with inflammatory mediators released by cartilage, bone and synovium interacting into the joint. Because obesity is a risk factor for OA in non-weight-bearing joints such as the hand, adipokines were suggested to play a role in OA. Starting from our work on the involvement of adipokines in OA, we address the hypothesis of a role of metabolic syndrome in OA progression. Metabolic syndrome-associated OA (MetS-OA) has recently been highlighted among the overall group of OA phenotypes, but the molecular mechanisms underlying the role of MetS in cartilage degradation has been poorly studied. Indeed, studies suggest that OA structural progression may result from altered communication between subchondral bone cells (e.g., osteoblasts, osteocytes) and cartilage cells (chondrocytes) and atheromatous vascular disease of subchondral bone.

In parallel, we have launched a cohort of patients (DIGICOD cohort) suffering from hand OA going to be followed at least 6 years in order to collect biological, imaging and clincal data to better understand the pathophysiology and the prognosis of this disease.

Four main projects are currently under investigation:

1 - Identify novel soluble mediators secreted by activated bone cells and acting on chondrocytes.

2 - Effect of hypertrophic differentiation of chondrocytes on remodelling of the osteochondral junction.

3 - Role of metabolic syndrome in OA beyond obesity.

4 - Preclinical/clinical validation of our in vitro or ex vivo discoveries.

Methodologies used

- Primary culture of articular chondrocytes (mouse, human) and costal chondrocytes (mouse), of murine osteoblasts (membrane 3D) and of human synoviocytes

- Control of chondrocyte phenotype (hypertrophic differentiation and fibroblastic dedifferentiation)

- Application of mechanical stress (cartilage explants and bone), Flexercell apparatus

- Bone/cartilage communication model (murine)

- Mesenchymal stem cells (from rat bone marrow)

-Cellular analysis (Western-blot, proteolytic activity, ELISA, qRT-PCR, ARN interference, immunocytology)

- Tissue analysis (histology paraffin, immunohistochemistry)

- Experimental model for Osteoarthritis (Mouse)

- Experimental model of tendon repair (Rat)