Research

Mechanistic Investigation of Osteoarthritis

Wnt signaling in OA

Wnt family are secreted factors that control a large number of cellular processes, including embryo development and disease pathogenesis. Several variants of Wnt signaling components were found to be associated with OA. However, prior reports of how Wnts regulate OA progression has resulted in conflicting results. We believe this could be due to the pleiotropic roles of different Wnt molecules on various tissues in the joint. We are investigating these roles by focusing on the OA-specific inflammatory and metabolic environment.

Macrolide and ghrelin signaling-inspired OA treatment strategies

Macrolide antibiotics, such as erythromycin, are small molecules with a macrocyclic lacton ring consisting of 14-16 carbons. We have found that macrolide antibiotic erythromycin could inhibit inflammatory cytokine-induced catabolism in chondrocytes in an antibiotic-independent manner and acted through the ghrelin signaling pathway. This led us to explore the potential of using macrolides and ghrelin as therapeutics for OA. In collaboration with Remedium Bio, we have also studied the efficacy of FGF18 as a new OA gene therapy. Our current research involves the understanding of the ghrelin signaling pathway in the joint as well as leveraging EM and ghrelin for attenuating OA progression.  

Glucose regulation of joint cartilage and skeletal growth

Dysregulated glucose metabolism is known to cause many diseases. Multiple reports pointed to a link of diabetes with OA, but others found this link tenuous. Considering OA primarily inflicts only weight bearing joints, we designed a versatile whole joint explant culture system (JM), to explore the effect of mechanical loading in varying biochemical conditions, including glucose levels. We found high levels of glucose synergies with mechanical stress to cause joint damage. Since disease recapitulates development, we also investigated glucose metabolic control on skeletal development and identified a critical switch of glycolysis to oxidative phosphorylation in controlling cartilage development.