The effect of inflammation on the course of experimental aseptic necrosis of femoral head

Abstract

Aseptic necrosis of the femoral head is a staged process in which osteodestruction is replaced by the bone repair. The outcome of this disease may be characterized by severe discongruence of the hip joint area, disability of the patient. Recently, the research interest is drawn to molecular and cellular mechanisms of bone homeostasis disorders and ways of its correction. A number of studies have demonstrated the role of nonspecific inflammation in pathogenesis of aseptic necrosis. However, a more detailed study of dynamic changes in the activity of osteogenesis signaling pathways is required. The aim of this study was to assess the role of molecular patterns of inflammation and osteogenesis during aseptic necrosis of femoral head in experimental model. Surgical induction of aseptic necrosis of the femoral head was performed in 16 rats, which were removed biweekly from experiment (by 4 animals), for 8 weeks. The expression of genes encoding proteins involved in osteogenesis regulation was studied by qPCR with reverse transcription. Concentration of VCAM1, MMP9 proteins was assessed by immunoblotting. The results of our study demonstrated heterogenous dynamics of changes in molecular and cellular disorders associated with bone homeostasis regulation in pathogenesis of aseptic necrosis. For the first two weeks after surgical procedure, the expression of HIF1α and TNFα genes, as well as the concentration of MMP9 and VCAM1 proteins, were determined as predictor factors. After 1 month, VCAM1 protein concentration and TNFα gene expression acted as protector factors, whereas IL6 gene and MMP9 protein were considered predictive factors. After 6 weeks, the development of aseptic necrosis was promoted by expression of the IL4 gene, and after 8 weeks, by IL6 gene. Thus, an important role in regulation of osteoresorption belongs to nonspecific inflammation, which can be triggered by acute tissue hypoxia. A significant effect of the inflammation process persists up to 8 weeks after induction of avascular necrosis of femoral head. Pathogenesis of bone destruction is associated not only with an increased activity of osteoclastogenesis, but also with a decreased intensity of osteoblastogenesis. In general, the molecular and cellular pattern of bone homeostasis disorders varies depending on the stage of aseptic necrosis.