Fig. 6.

Effects of intra-synovial injections of CaSR antagonist (NPS2143) and agonist (Cinacalcet) on morphology (A), gene (B) and protein expression (C) in rat TMJ-cartilage without (Control) or with UAC stimulation. Test compounds (50 μl of 100 nM stock) and vehicle injections were performed on 10 weeks old rats every other day 2 days for 4 weeks. UAC began 4 weeks before drug injections and continued for another 4 weeks during drug treatments. (A) Safranin O staining (in red) showed the ability of NPS2143 to increase proteoglycan content and thickness of TMJ-cartilage and decreased OA grade, the ability of Cinacalcet to suppress these parameters in both control and UAC groups when compared to corresponding vehicle-injected group. Bar=100μm. n=6 rats per group. (B) qPCR analyses of mRNA and (C) immunoblotting analysis of Col-II and Aggrecan protein extracted from the TMJ-cartilage of the above mice showed the ability of NPS2143 to increase the expression of early differentiation markers and to suppress expression of terminal differentiation makers in both control and UAC groups when compared to corresponding vehicle-injected group and vice versa for effects of Cinacalcet. Six TMJ-cartilages were pooled into 3 samples (2 cartilage per sample) for qPCR and immunoblotting analysis. All values in (B) and (D) were normalized to the Control-Vehicle. Values are presented as the mean±SD. **p<0.01, *p<0.05 between groups as specified by top horizontal bars in each panel.