High glycine concentration increases collagen synthesis by articular chondrocytes in vitro: acute glycine deficiency could be an important cause of osteoarthritis

Abstract

Collagen synthesis is severely diminished in osteoarthritis; thus, enhancing it may help the regeneration of cartilage. This requires large amounts of glycine, proline and lysine. Previous works of our group have shown that glycine is an essential amino acid, which must be present in the diet in large amounts to satisfy the demands for collagen synthesis. Other authors have shown that proline is conditionally essential. In this work we studied the effect of these amino acids on type II collagen synthesis. Bovine articular chondrocytes were cultured under a wide range of different concentrations of glycine, proline and lysine. Chondrocytes were characterized by type II collagen immunocytochemistry of confluence monolayer cultures. Cell growth and viability were assayed by trypan blue dye exclusion method. Type II collagen was measured in the monolayer, every 48 h for 15 days by ELISA. Increase in concentrations of proline and lysine in the culture medium enhances the synthesis of type II collagen at low concentrations, but these effects decay before 1.0 mM. Increase of glycine as of 1.0 mM exceeds these effects and this increase continues more persistently by 60–75%. Since the large effects produced by proline and lysine are within the physiological range, while the effect of glycine corresponds to a much higher range, these results demonstrated a severe glycine deficiency for collagen synthesis. Thus, increasing glycine in the diet may well be a strategy for helping cartilage regeneration by enhancing collagen synthesis, which could contribute to the treatment and prevention of osteoarthritis.

Human skeletal muscle CD90+fibro-adipogenic progenitors are associated with muscle degeneration in type 2 diabetic patients

“…This effect is likely not restricted to PDGF-AA but true for other stimulators of ECM protein formation such as TGFb1 4 thereby linking ECM protein synthesis to enhanced reliance on glycolysis. Increasing glycolytic flux and lactate production not only delivers ATP, but is also key for essential aspects of collagen formation such as glycine synthesis and collagen hydroxylation 4,67,68 . In contrast, cell proliferation was not dependent on glycolysis in agreement with previous studies 69 .…”

Proline-dependent regulation of collagen metabolism

“…Although several lines of evidence suggest that Pro is conditionally essential amino acid that must be present in diet to support collagen biosynthesis, recent studies provided evidence that glycine is as well as important in diet to satisfy the demands for the process [56]. However, it has been found that milimolar concentration of glycine is required to enhance type II collagen in bovine chondrocytes, while Pro and lysine evoked the effect at physiological concentrations [56].…”

Impact of Bovine Diet on Metabolomic Profile of Skim Milk and Whey Protein Ingredients

“…Concentrations of glycine in GRS-derived acid whey were significantly higher than those from TMR, while concentrations were significantly higher in sweet whey derived from both pasture-based systems when compared to TMR. Glycine is a nonessential proteinogenic AA, primarily utilized in the synthesis of collagen, with limited function in the synthesis of other proteins and metabolic pathways [22]. Previous work by Meléndez-Hevia and de Paz-Lugo [23] suggests that a restriction in the stoichiometry of the glycine synthesis reaction may lead to insufficient glycine production relative to metabolic demand, making glycine an essential or conditionally essential AA.…”