Given previous reports have shown that mast cells obtained from osteoarthritic synovial tissues express activating FcRs (e.g., FcγRI) as well as FcεRI at levels similar to those seen in rheumatoid arthritis (Lee et al., 2013), we propose a model wherein the IgE/FcεRI/Syk signaling axis in mast cells potentiates chronic inflammation in osteoarthritis. The gene discussed is FCER1A; the disease is rheumatoid arthritis.