Metabolic pathways and control mechanisms involved in the biosynthesis and turnover of collagen in normal and pathological connective tissues

Abstract

Abstract. The biosynthesis of collagen molecules and their subsequent assembly into fibers involves a complex series of post‐ribosomal modifications which occur intracellularly and extracellularly. Some of these subtle alterations lead to the formation of intramolecular and intermolecular cross‐links, whereas others seem to dictate the 3‐dimensional organization of the collagen fibers. For their normal function, tissues require an optimum amount of collagen and proteoglycans. Such a balance coupled with specificity built into collagen seems to assure adequate function. Changes in the rates of synthesis, turnover or transcription of genetic information which affect the type of collagen deposited at a particular site may lead lo a stale of disease. It is hoped that our current understanding of such mechanisms, coupled with our ability to inhibit or accelerate some of these processes, will allow us lo effectively control the metabolism of connective tissues.

Gene expression and extracellular matrix ultrastructure of a mineralizing chondrocyte cell culture system.

“…While the mechanism by which ascorbic acid promotes chondrocyte differentiation is unclear, it is well documented to be essential in maintaining normal extracellular matrices and in promoting maximal collagen synthesis in connective tissues (11,12,40,53,57,58,59). The role of ascorbate in proline and lysine hydroxylation has been extensively demonstrated (48), and its absence during collagen synthesis in a wide variety of cultured cells has been shown to result in diminished rates of collagen synthesis and high rates of collagen turnover (45). The data presented here clearly show that ascorbic acid increases both total collagen synthesis (from 30-100 % depending on the nutrient medium) and total collagen deposition.…”

Collagen Development in Granulation Tissue as Compared With Collagen of Skin and Aorta From Injured and Non‐injured Rats

“…Recent years have brought evidence of biochemical differences between collagens from various tissues. These differences include variations in the amino acid composition, the degree of hydroxylation of proline and lysine, the degree of glycozylation of OH-lysine, as well as differences in the type and stability of the intermolecular cross-links in collagen (Nimni 1973, Bailey et al 1974, Bornstein 1974. The knowledge of these tissue differences may lead to a better understanding of differences in the reactivity of various tissues, and may also open the possibility of a more specific pharmacological influence on the various connective tissues.…”