Dr. Kathleen Sluka
Participation year
Project title

Determining the Role of Acid Sensing Ion Channel 3 in Fibroblast Like Synoviocyte Apoptosis


Rheumatoid arthritis (RA) is a chronic autoimmune joint disease characterized by inflammation and joint hyperplasia. Fibroblast-like synoviocytes (FLS) are key cellular participants in the pathogenesis of RA. Normally, FLS provide a thin lining of the synovial membrane. In RA, FLS over-proliferate and thicken the synovial lining, leading to diminished joint activity and joint damage. Acid sensing ion channels respond to decreases in pH and we previously showed expression of ASIC3 in FLS. ASIC3-/- knockout (KO) mice have enhanced inflammation scores, increased synovial lining thickening, and greater bone erosion when compared to WT controls (unpublished observations). We hypothesize that ASIC3 controls excessive inflammation in normal animals by causing cell death of synoviocytes. To further study this, wild-type and ASIC3-/- KO FLS cells were used to determine if apoptosis ensues in response to pHs below the physiological level. Cells underwent overnight serum starvation followed by a 24-hr pH treatment using pH 6.0 or pH 7.4 medium, as a model environment of how FLS respond in inflamed or normal pH environments. Cell death was measured in FLS using the LIVE/DEAD assay (Invitrogen). Results strongly support the hypothesis that ASIC3 is involved in cellular apoptosis in FLS. We suggest that ASIC3 is protective against RA by limiting synovitis, reducing inflammation, and mediating cellular apoptosis.

Willie  Frazier
Virginia Tech