Our group studies pseudoachondroplasia (PSACH), a severe dwarfing condition associated with severe and osteoarthritis early-onset. Using our pseudoachondroplasia mouse model, we defined the mechanisms underlying chondrocyte dysfunction and loss, ER stress, inflammation, oxidative stress. This becomes a self-perpetuating pathological process, with each pathologic component exacerbating the others (inflammation, ER and oxidative stress). This persistent-mutant-COMP driven ER stress should activate autophagy clearance or proteasomal degradation. However, in contrast, we found that the inflammation and ER stress over stimulates mTORC1 shutting down autophagy. To Based on all of these results, We showed that antioxidants/anti-inflammatory therapeutics interrupt this self-perpetuating stress loop dampening the mutant-COMP growth plate chondrocyte pathology. Resveratrol is currently being tested in a phase 1 PSACH clinical trial.
Our pseudoachondroplasia mouse model has lead us to expand my work into the field of osteoarthritis because early-onset osteoarthritis is associated with this dwarfing condition. The inducible feature of the model allows the stimulation of ER stress in adult articular chondrocytes in order to assess the role that ER stress plays in osteoarthritis establishment and progression. Our recent findings suggest that ER stress may be a major component in idiopathic osteoarthritis opening the door for treatment/prevention strategies.
Current interests include:
- Cartilage Health
- Treatment strategies to prevent joint damage