Okada Yosuke, Tanikawa Takahisa, Iida Takeshi, Tanaka Yoshiya
University of Occupational and Environmental Health, Japan.
Clin Calcium. 2007 Jun;17(6):872-7.
Idiopathic osteonecrosis of the femoral head (IONF) is known to be caused by tissue ischemia, which is mainly associated with high-dose glucocorticoid (GC) used for the treatments of systemic autoimmune diseases. However, precise pathological mechanisms of IONF remain unclear. We first found that hypoxia-inducible factor (HIF) -1alpha, a major transcription factor rapidly induced under hypoxic conditions, was highly expressed on endothelial cells of femoral head in patients with IONF. Transfection of HIF-1alpha induced p21-mediated arrest of cell cycle and subsequent apoptosis in endothelial cells. High dose GC also induced cell cycle arrest and apoptosis. Furthermore, there were additional effects between HIF-1alpha and high dose GC for the growth arrests and apoptosis of the cells. However, C-type natriuretic peptide (CNP) inhibited both cell cycle arrest and apoptosis of the endothelial cells in a concentration-dependent manner. There results indicate that hypoxia and high-dose GC play a pivotal role for vascular injury and that CNP could have a potential to protect the vascular injury seen in patients with IONF.
股骨头缺血性坏死（IONF）已知是由组织缺血引起的，这主要与用于治疗全身性自身免疫性疾病的高剂量糖皮质激素（GC）有关。然而，IONF的确切病理机制仍不清楚。我们首先发现，缺氧诱导因子（HIF）-1α是在缺氧条件下迅速诱导产生的主要转录因子，在IONF患者的股骨头内皮细胞上高度表达。转染HIF-1α可诱导p21介导的内皮细胞细胞周期停滞及随后的凋亡。高剂量GC也可诱导细胞周期停滞和凋亡。此外，HIF-1α和高剂量GC对细胞生长停滞和凋亡还有额外的协同作用。然而，C型利钠肽（CNP）以浓度依赖的方式抑制内皮细胞的细胞周期停滞和凋亡。这些结果表明，缺氧和高剂量GC对血管损伤起关键作用，而CNP可能具有保护IONF患者血管损伤的潜力。
