Combinatorial PRG4 and IL-1Ra gene therapy induces protective expression changes in anabolic and catabolic genes. Whole joints were collected from CLT mice, and RNA expression was analyzed by Real Time PCR three weeks postinjection. (A) Expression of anabolic and matrix genes, including Prg4, Tgfb1, and Acan, were elevated in combinatorial and HDV-EF1-Prg4-treated animals, whereas there was no effect on Col2a1 expression. (B) Expression of hypertrophy marker Col10a1 was maintained in combinatorial and HDV- NFκB-Il-1ra-treated animals, whereas HDV-EF1-Prg4 and empty HDV-treated mice exhibited elevated expression. Inflammatory genes Il-1b, Il-6, and Ptgs2 showed a protective expression pattern in combinatorially treated animals. Data are represented as mean + SD. n = 3 *p < 0.05 ANOVA.