EARLY STAGES OF REGENERATION HISTOGENESIS IN PERIOSTAL PART OF BONE CALLUS IN MAN

Objective - to study the intercellular interactions during early stages of reparative osteohistogenesis. Materials and methods. The object of the study were fracture hematomas, which were obtained from patients of both sexes aged 15-84 years in the course of reconstructive treatment during the first 12 days after the fracture. Results. The earliest event of bone reparation was the migration to the fracture area of a heterogeneous macrophage population with an active cytokine-synthetic function that resulted in the formation of a local pool of VEGF-producing cells in the hematoma and preceded the appearance of the first thin-walled vessels among the tissue detritus. High mitotic activity of the endothelial cell elements in conjunction with the membrane expression of Flk-1 reflected a close molecular interaction between endothelial cells and cytokine-producing macrophages. The active process of angiogenesis occured in parallel with a rapid increase in the amount of connective tissue. By 12 days, a significant decrease in the total number of vessels was noted, which, together with a decrease in mitotic activity of endotheliocytes, reflected a decrease in angiogenesis activity at the time of formation of the structures of woven bone. Expression of Flk-1 and Flt-4 receptors in osteoblastic cells indicated a cytokine regulation of the processes of bone tissue histogenesis. Conclusion. At the early stages of reparative osteogenesis, VEGF-VEGFR regulatory axis was shown to play a key role in the coordination of intercellular molecular interactions, ensuring a consistent replacement of cell-tissue populations in fracture hematoma.

VEGF, fracture hematoma, reparative histogenesis, angiogenesis, VEGF