MOLECULAR ASPECTS OF BONE REMODELING

Abstract

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Introduction. About 33.8% of women and 26.9% of men over 50 years suffer from osteoporosis in the Russian Federation (according to the Institute of Rheumatology of the Russian Academy of Sciences). Idiopathic postmenopausal or senile osteoporosis is most common (85% of cases), resulting in bone remodeling disorders. Therapy of osteoporosis requires a deep understanding of the basics of physiological regeneration of bone tissue. Purpose. Identification of the key links in the regulation of bone tissue remodeling. Materials and Methods. Analysis and systematization of literary sources. Results. It was revealed that sclerostin indirectly blocks the effects of bone morphogenetic proteins (BMPs) via the Wnt - signaling cellular pathway. In people with impaired formation of sclerostin, sclerosteosis develops (a pathological proliferation of the bony tissue of the facial skeleton). It is also known that the RANKL (receptor activator of nuclear factor kappa - B ligand) - OPG (osteoprotegerin) - the cytokine system plays a key role in conjugation of the remodeling phases. Numerous cytokines and hormones stimulate or inhibit the effects of RANKL and OPG. Some interleukins, prostaglandins E and E2, TNF (tumor necrosis factor), M - CSF, GM - CSF (macrophage and granulocyte - macrophage colony - stimulating factors) are local factors of bone resorption; interferon gamma, transforming growth factor beta (TGF - beta) are local factors of bone osteogenesis. Several factors have been studied separately or together in a number of investigations in vivo and in vitro, but with conflicting results. Regulation of calcification of bones is actively studied. According to recent data, inorganic pyrophosphate can act as a calcification inhibitor. The inhibitory effect of pyrophosphate is eliminated by pyrophosphatase during mineralization, which is found in bone tissue. Conclusion. The recent scientific data on the regulation of bone tissue regeneration, that showed good results in clinical trials, made it possible to develop new directions in the therapy of osteoporosis: the use of antibodies to RANKL (Denosumab) and antibodies to sclerostin (Romosozumab).