Fig. 4

The impact of recombinant human proteoglycan 4 (rhPRG4) treatment on interleukin-1 beta (IL-1β)-induced osteoarthritis fibroblast-like synoviocytes (OA FLS) proliferation and regulation of proteoglycan-4 (PRG4) gene expression and production. Data are presented as the average ± standard deviation of four independent experiments; *p < 0.001, **p < 0.05. a Impact of rhPRG4 treatment (50, 100, and 200 μg/ml) on IL-1β-induced proliferation of OA FLS over 48 hours. IL-1β induced OA FLS proliferation. rhPRG4 (100 and 200 μg/ml) reduced IL-1β-induced OA FLS proliferation. Co-treatment with a CD44 neutralizing monoclonal antibody (CD44 Ab) abolished the effect of rhPRG4 treatment. CD44 Ab treatment alone did not alter IL-1β-induced OA FLS proliferation. b Regulation of PRG4 production by cytokines in OA FLS and rheumatoid arthritis FLS (RA FLS). OA FLS produces significantly higher PRG4 protein compared to RA FLS. IL-1β and TNF-α reduce PRG4 production by OA FLS while transforming growth factor beta (TGF-β) increases PRG4 production by OA FLS. IL-1β, TNF-α, and TGF-β did not alter PRG4 production by RA FLS. c IL-1β downregulated PRG4 gene expression in OA FLS. PRG4 expression in the IL-1 β + rhPRG4(100 μg/ml) group was higher than PRG4 expression in the IL-1β alone group and was not different from PRG4 expression in control cells. PRG4 expression in the IL-1β + rhPRG4(200 μg/ml) group was lower than PRG4 expression in the control and in the IL-1β + rhPRG4(100 μg/ml) group. rhPRG4 (200 μg/ml) treatment reduced basal PRG4 gene expression in OA FLS compared to control. Data are presented as fold change compared to untreated control OA FLS