Dynamics of the Expression of Bone Homeostasis Genes in the Developmet of Aseptic Necrosis of the Femoral Head in the Experiment

Abstract

The pathogenesis of a number of diseases is characterized by a violation of the regulation of bone homeostasis, with the progressive development of osteodestruction. At the same time, an active study of the mechanisms leading to a shift in the balance of osteoreparative and osteoresorption directions of osteogenesis is underway. The determination of molecular and cellular patterns affecting the dynamics of changes in bone metabolism is a significant task among a wide range of specialists. Such research works allow us to propose algorithms for targeted therapeutic effects on various key links in the pathogenesis of osteodestruction. The study analyzed the expression of genes involved in maintaining bone homeostasis, changes in the histological picture under experimental conditions, depending on the time elapsed since the induction of aseptic necrosis. The result of the work showed the heterogeneity of the development of osteodestruction in an experiment on Wistar rats, with a surgically created focus of hypoperfusion of the femoral head against the background of increased intra-articular pressure. In the first two weeks of the development of aseptic necrosis, the expression of the hif1a gene was most actively determined, which can be considered from the position of a trigger for further disruption of bone metabolism. At the same time, the concentration of m-RNA of osteogenesis and osteoresorption genes was reduced. The most active osteolytic processes according to electron microscopy data, increases in the expression of osteoclastogenesis induction genes were observed at 6 weeks of the experiment. The osteoreporative orientation of bone metabolism gradually increased from the beginning of the study and 2 months after the manifestation of avascular necrosis of the femoral head, active osteoblasts, increased expression of bone matrix genes, osteoblastogenesis were determined. Thus, the development of osteodestruction is an extremely heterogeneous process, with dynamically changing molecular patterns depending on time, determining the activity of signaling pathways of bone metabolism.