Role of Type I Collagen in
Osteogenesis

Role of Type I Collagen in Osteogenesis

Type I collagen creates layers of fibrils in the extracellular matrix of bone, giving bone its tensile strength and forming a template for the deposition of inorganic minerals. Type I collagen owes its ability to form fibrils to its very specific amino acid sequence. Both the alpha1 chain encoded by COL1A1 and the alpha2 chain encoded by COL1A2 are built from 338 uninterrupted repeats of the amino acid sequence Glycine-X-Y, where X is often proline and Y is often hydroxyproline. Due to the regular pattern of prolines and hydroxyprolines, the alpha chains assume a left-handed helical conformation. Two alpha1 helices and one alpha2 helix then wind around each other to form a right-handed triple helix. Presence of a glycine in every third position is critical for triple helix formation, since only glycine, the smallest of all amino acids, fits into the confined space in the center of the triple helix.

Triple helix formation starts at the C-termini of the alpha chains and proceeds toward the N-termini in a zipper-like fashion. Prior to and simultaneously with triple helix formation, prolines and lysines in the alpha chains are chemically modified by addition of hydroxyl or sugar groups. These modifications are believed to play a role in triple helix stabilization. Completed triple helices are secreted from the cells and spontaneously assemble into collagen fibrils.