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. 2019 May 14;8:e39905. doi: 10.7554/eLife.39905

Figure 5. A critical role for IgE-mediated signaling through FcεRI and Syk in osteoarthritis.

(a–d) Cartilage degradation in medial regions of stifle joints from C57BL/6J FcεRIα-sufficient (Fcer1a+/+,n = 8) and FcεRIα-deficient (Fcer1a-/-,n = 8) mice 20 weeks after DMM surgery. Representative safranin-O stained medial stifle joint sections from these mice are shown; arrowheads show severe cartilage loss. Cartilage degradation (b), osteophyte formation (c), and synovitis (d) in medial regions of stifle joints from these mice are quantified. Symbols represent scores from individual mice. Bars denote mean ± s.d. *p≤0.05, **p≤0.01, by Mann Whitney test. Scale bars, 200 μm. Scoring of joint pathologies was done by two investigators blinded to experimental groups. Data are representative of two independent experiments with similar results. DMM, destabilization of the medical meniscus. (e–h) Cartilage degradation in medial regions of stifle joints from C57BL/6J mice subjected to DMM surgery and then orally with vehicle (n = 6) or 75 mg/Kg/day of the Syk inhibitor PRT062607 (n = 7), for 12 weeks. Representative Safranin-O stained medial stifle joint sections from these mice are shown (e); arrowheads show severe cartilage loss. Cartilage degeneration (f), osteophyte formation (g), and synovitis (h) in medial regions of stifle joints from these mice are quantified. Symbols represent scores from individual mice. Bars denote mean ± s.d., **p≤0.01, by Mann Whitney test. Scale bars, 200 μm. Scoring of joint pathologies was done by two investigators blinded to experimental groups. (i) Relative mRNA expression of pro-inflammatory/degradative enzyme genes in mouse stifle joints. Data are representative of two independent experiments with similar results. DMM, destabilization of the medical meniscus.

Figure 5.

Figure 5—figure supplement 1. Deficiency in FceR1a or blockade of FcεRIα signaling in mice reduces synovitis and osteophyte formation following DMM.

Figure 5—figure supplement 1.

(a) Representative H&E-stained knee joint sections from Fcer1a-sufficient (Fcer1a+/+) and Fcer1a-deficient (Fcer1a-/-) mice 20 weeks after DMM surgery. (b) Representative H&E-stained knee joint sections from C57BL/6J mice treated orally with vehicle (PBS), or the Syk inhibitor PRT062607 (75 mg/Kg/day) every day for 12 weeks following DMM surgery. Osteophytes (yellow arrows) and synovial thickening (open arrows) were prominent in vehicle-treated controls, but not in the PRT062607-treated mice. Scale bars, 200μm.