INSTITUTO DE INMUNOLOGIA, GENETICA Y METABOLISMO
Unidad Ejecutora - UE
capítulos de libros
Type I Collagen and its utility as specific bone marker
FRIEDMAN S; - HERNÁNDEZ EVELYN; SUAREZ C; FERREIRA MONTEIRO A; GONZALES CHAVES M; PELLEGRINI G; RODRIGUEZ P; ZENI S; FRIEDMAN SN
Type I Collagen: Biological Functions, Synthesis and Medicinal Applications
Lugar: NY; Año: 2012;
Collagens are proteins centrally involved in the formation of fibrillar and microfibrillar networks of the extracellular matrix. The biosynthesis of collagens starting with gene transcription within the nucleus, to the aggregation of collagen heterotrimers into large fibrils is a complex multistep process. It is characterized by the presence of a large number of co- and post-translational modifications, many of them being unique to collagens or collagen-like proteins. The fibril-forming collagens are synthesized as procollagens which is released to the extracellular space where undergo several modifications: removal of large procollagen N- and C-terminal peptides, ordered aggregation, crosslink formation. Biochemically, collagen is composed of a triple helix which consists of three α-chains. The amino acid composition of collagen is atypical for proteins, particularly with respect to its high hydroxyproline (Hyp) content. However, their size, function and tissue distribution vary considerably among collagens. To date, more than twenty genetically distinct collagen types have been described; being type I collagen the most abundant and best studied collagen of the body. It forms more than 90% of the organic mass of bone and is the major collagen of tendons, skin, ligaments, cornea, and many interstitial connective tissues with the exception of very few tissues such as hyaline cartilage, brain, and vitreous body. The collagen type I triple helix is usually formed as a heterodimer by two identical α1(I)-chains and one α2(I)-chain. In most organs and notably in tendons and fascia, type I collagen gives tensile stiffness and in bone, it defines substantial biomechanical properties regarding load bearing, tensile strength, and torsional stiffness in particular after calcification. The post-translational modifications of the collagenous matrix are important for both its structural and mechanical properties, and disruption of the cross-linking can result in severe dysfunction of the tissue. Both, biosynthesis and breakdown products are used in medicine as specific and sensitive bone markers to evaluate bone remodelling. In this regard N-terminal procollagen type I (PICP) is used as a bone formation marker while the crosslinks and the N and C-telopeptides (NTX and CT, respectively) are used as bone resorption markes.