Localization of VEGF, TGF-β1, BMP-2, and Apoptosis Factors in Hypertrophic Nonunion of Human Tubular Bones

We studied localization of VEGF, TGF-β1, BMP-2, caspase-3, Bcl-2, and TNFα in the callus samples obtained from 5 patients (4 women and 1 man) aged 41-53 years during planned surgery for nonunion and pseudarthrosis of the clavicle (n=1), ulna (n=1), femur (n=1), and tibia (n=2) bones. Two control groups included material of hypertrophied callus (n=3) with consolidated fractures of long bones and samples of intact bones (n=3) obtained by postmortem autopsy of subjects without pathology of the musculoskeletal system. A nonuniform distribution of the studied markers was revealed. Active expression of VEGF was observed in fibroblast-like cells of the fibrous tissue, osteoblasts of the periosteum and osteons. Osteoblasts expressing BMP-2 were localized in the periosteum and the loose connective tissue of the Haversian canals. The number of immunopositive cells expressing TGF-β1 and TNFα in the callus exceeded that in the control and correlated with the expression of caspase-3 in fibroblast-like cells, osteoblasts, chondroblasts, and microvascular endotheliocytes. The results allow considering fracture nonunion as a result of overproduction of cytotoxic and proapoptotic factors in chronic inflammation and dysfunction of the expression of morphogenetic proteins. The morphochemical patterns of the studied markers open up prospects for the development of new methods of pharmacological correction of fracture repair.