Hypoxia increases insulinlike growth factor gene expression in rat osteoblasts

Vascular disruption secondary to fracture leads to a hypoxic zone of injury where the oxygen tension at the center of the wound is quite low. In this dynamic microenvironment, a number of growth factors are elaborated to stim ulate the synthetic processes of fracture repair. Previously the authors ha ve shown the hypoxia-induced increase of vascular endothelial growth factor expression in osteoblasts. The purpose of these experiments was to examine osteoblast expression of insulinlike growth factors (IGF) I and II-cytokin es believed to play a role in increased collagen synthesis, chemotaxis, and proliferation of osteoblasts in response to hypoxia. Primary cell cultures of osteoblasts isolated from neonatal rat calvaria were subjected to hypox ia (PO2 = 35 mmHg) for 0, 3, 6, 24, and 48 hours. Northern blot analysis of ribonucleic acid (RNA) from resulting cultures demonstrated a more than 60 % increase in IGF-II messenger RNA (mRNA) expression after 3 hours of hypox ia. IGF-II mRNA expression continued to increase through later time points to 200% and 260% of baseline at 24 and 48 hours respectively. In contrast, IGF-I demonstrated no significant change in mRNA expression compared with b aseline control (normoxia) cultures. In these experiments the authors have demonstrated a hypoxia-induced increase in IGF-II but not IGF-I in primary osteoblasts. The differential expression of these two growth factors may un derscore important differences in the behavior of osteoblasts in the hypoxi c fracture microenvironment. Taken together, these data add additional supp ort to the theory that hypoxia induces gene-specific changes in expression of molecules important to extracellular matrix formation for successful bon e healing.