Fig. 1. Both exogenous FXIIIA and TG2 induce chondrocyte hypertrophic differentiation. We studied induction by TG2 and FXIIIA of MMP13, VEGF and type X collagen in cultured chondrocytes. Normal human knee articular chondrocytes plated in 12-well dishes (at 10⁵ cells per well) were incubated for 4 or 8 hours with 100 ng/ml of recombinant WT TG2 or FXIIIA in the ascorbate-containing medium A described in Materials and Methods. (A) Quantitative PCR. Using quantitative RT-PCR, we determined chondrocyte GAPDH mRNA expression levels relative to those of MMP13 and VEGF, and the mRNA expression ratio of type X collagen to type II collagen, studying data collected from three separate human donors (n=9, ^*P<0.05). (B) Bovine articular cartilage explants. Assessment of the induction by TG2 and FXIIIA of type X collagen in cartilage organ culture. Normal bovine articular cartilage explants in organ culture were incubated with 100 ng/ml recombinant WT TG2 or FXIIIA for 5 days in medium A, and frozen 10-µm sections were stained for expression of type X collagen (representative of five donors).