Type II collagen is synthesized as a procollagen molecule, with N-propeptides and C-propeptides at each end. It is produced in two isoforms by alternative RNA splicing. One form (PIIANP) includes, and the other form PIINP excludes, a 69-amino-acid globular domain in the N-propeptide that is encoded by exon 2. During synthesis, these propeptides are removed by specific proteases before the mature molecules are incorporated into fibrils. The C-propeptide can be detected by a PIICP assay. IGF-I significantly induced collagen type II formation at low and intermediate catabolic insult, but not at maximal insult. In the bovine articular cartilage explants, IGF-I induced an increase in PIINP level up to 4.8+/-1.1[ng/ml]/mg cartilage whereas CTX-II remained below 0.1+/-0.1[ng/ml]/mg cartilage. In the catabolic stimulated explants both PIINP and CTX-II were released to the supernatant, reaching concentrations of 9.0+/-1.4 and 9.1+/-2.2[ng/ml]/mg cartilage, respectively.