Cellular mechanisms of age-dependent bone remodeling

Abstract

The structural integrity of the skeleton is ensured by the constant remodeling of bone tissue, which is based on the functioning and interaction of osteolytic cells (osteoclasts) and bone tissue forming cells (osteoblasts/osteocytes). Despite the general understanding that the degree of mineralization of the bone matrix determines the fragility of the skeleton, there is currently insufficient information about its age-related changes associated with the functioning of these cells. The purpose of the review is to evaluate existing data on age-related bone changes associated with the functional state of mesenchymal stem cells, osteoblasts/osteocytes and osteoclasts. Inclusion criteria: randomized or non-randomized controlled studies examining age-related bone change. A search for studies in the field of bone tissue condition was carried out in electronic scientific databases Google Scholar, Medline, PubMed, Scopus, Web of Science and Cochrane Library by keywords and their combinations using the AMSTAR 2 program. The selection of publications (59 out of 680 included) was carried out randomly, after which three authors independently assessed their methodological quality. The main pathogenetic mechanism involved in bone loss with age is a decrease in the formation of osteoblasts with impairment of their ability to osteogenic differentiation. Osteocytes in old age are subject to excessive and prolonged stress, which causes unbalanced autophagy and apoptosis, which leads to changes in their ability to deposit and mineralize extracellular organic matrix. With age, accelerated osteoclastogenesis occurs, mediated by osteoblasts, which leads to increased expression of certain receptors at the level of bone stromal cells and osteoblasts. The presented literature data demonstrate convincing evidence that an increase in bone resorption due to complex metabolic processes with age occurs against the background of an increase in the number and activity of osteoclasts, apoptosis of osteoblasts with a decrease in their metabolic activity, as well as a redistribution of osteogenic differentiation of mesenchymal stem cells towards adipocytes. The results presented in the review can be used as a basis for developing diagnostic criteria for identifying senile osteoporosis and the risk of fractures.