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, N-terminal pro-peptide of pro-collagen type II) 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.