| Avascular necrosis of the femoral head (ANFH) is manifested terminally by death of bone cells that results in impairment of normal reparative processes along microfractures in the femoral head. The understanding of its pathophysiology and its progression is important as we are currently unable to predict who will develop ANFH. Amongst several pathogenic mechanisms, the vascular hypothesis is the most compelling in which, decrease in local blood flow in the femoral head has a pivotal role in the pathogenesis of ANFH.;Although ANFH pathogenesis is presumed to involve multiple hits, it is well known that ANFH tends to develop after exposure to glucocorticoids (GC), one of the major risk factors for this condition. It is known that GC have direct and indirect effects on cells. The direct effects, in particularly apoptosis of osteoblast and osteocyte, appears in our studies to play a predominant role in the pathogenesis of ANFH.;We characterized an inbred rat strain (Wistar Kyoto) susceptible to develop steroid-induced osteonecrosis. We tested the hypothesis that GC contribute to a differential gene expression in the femoral head of rats with early ANFH versus placebo-treated rats. Rat exon array, confirmed by real time PCR amplification, demonstrated a significant upregulation of a number of specific genes, particularly alpha-2-macroglobulin. Besides, several genes involved in the dynamic remodeling structure of the femoral head were differentially expressed suggesting that if the balance between degradation and repair (bone remodeling) became shifted to degradation and bone loss, a failure of structural integrity at the subchondral region could occur.;Together, our findings suggested that glucocorticoid-induced ANFH in rats might potentially be mediated at least in part, by a specific gene sharing hemostatic, osteogenic and cartilage properties.;Dysregulation of endothelial cell (EC) activating factors and stimulators of angiogenesis, EC damage, EC apoptosis, regional endothelium dysfunction and thrombophilia, particularly impaired fibrinolysis, could lead to microvascular thrombosis important in vascular hypothesis. |
