Matrilin-3 (MATN3) maintains the expression of key cartilage extracellular matrix (ECM) genes. Recombinant human (rh) MATN3 treatment maintains type II collagen (COL2A1) gene expression in the presence and absence of IL-1β in C28/I2 cells (A) and primary human chondrocytes (PHCs) (B) at 8 hours. MATN3 also inhibits the IL-1β-induced downregulation of aggrecan (ACAN) gene expression in PHCs at 36 hours (C). Whole limb mRNA analysis of newborn MATN3 knockout (KO) mice of the C57BL/6J background reveal lower basal gene expression of Col21a and Acan compared to wild-type mice of the same genetic background (D). For all cell culture experiments, rh MATN3 protein is used at 200 ng/ml. Rh IL-1β protein treatment is always 5.0 ng/ml. *Significant differences (P ≤ 0.05) from the untreated control group; #significant differences (P ≤ 0.05) from the IL-1β only treated group. For cell culture experiments, data are representative of three individual experiments (n = 5 for mouse whole limb mRNA studies).