Calcium and collagen biosynthesis: systematic analysis of molecular mechanisms of action
Gromova O.A.¹, Torshin I.Yu.², Tomilova I.K.¹, Gilels A.V.³, Demidov V.I.<sup>1

1</sup> Ivanovo State Medical Academy
² Moscow Institute of Physics and Technology, Dolgoprudny
³ RHANA Medical Corporation, Moscow

Introduction: Adequate level of collagen biosynthesis is one of the most important indicators of normal physiological metabolism of connective tissue. Fundamental and clinical trials revealed that increased level of extracellular calcium stimulates collagen synthesis/secretion.
Objective: To investigate molecular mechanisms of calcium influence on collagen synthesis/secretion.
Material and Methods: systemic biological analysis of calcium-dependent proteins of human proteome with functional relationships method.
Results: The most relevant molecular mechanisms of calcium ions influence on collagen biosynthesis are supported by Ca-sensing receptor (CASR) and bone morphogenetic protein-4 (BMP4). CASR expression in cartilage and bone tissue directly regulates skeletal homeostasis and connective tissue metabolism. CASR is a physiological regulator of growth, differentiation and survival of fibroblasts, osteoblasts and osteoclasts. These cells produce all components of connective tissue - collagen fibers, elastin fibers and proteoglycans of jelly medium. CASR promotes fibroblasts and osteoblasts segmentation, which increases activity of collagen tissue cells and collagen biosynthesis. BMP4 induces cartilage and bone production, teeth growth and fracture healing. Increased extracellular calcium stimulates an increase of osteoblasts quantity and inhibits osteoclast formation, by impact on BMP levels of expression. In addition, bone metabolism and collagen biosynthesis need the support of osteotropic micronutrients. Collagen biosynthesis requires Ca2+, Mg2+, Fe2+, Mn2+, Zn2+, Cu+ as cofactors for corresponding enzymes. The analysis also revealed adverse effects of calcium channel blockers that inhibit collagen-I synthesis and secretion by fibroblasts.
Conclusions: The analysis shows perspective ways to improve the efficacy of calcium supplementation for nutritional support of bone metabolism. Collagen biosynthesis improvement is an obligatory compound of bone structure restoration in fracture healing, bone regeneration in postmenopausal and drug-related osteoporosis and other cases of violations of bone integrity. Collagen biosynthesis normalization contributes to better calcium retention in the bone tissue and increase of bone mineral density.

Key words: collagen biosynthesis, calcium homeostasis, bone morphogenesis, connective tissue, Calcemin.

For citation: Gromova O.A., Torshin I.Yu., Тоmilova I.К. et al. Calcium and collagen biosynthesis: systematic analysis of molecular mechanisms of action // RMJ. 2016. № 15. P. 1009–1017.