Department of Orthodontics and Craniofacial Developmental Biology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
Biochem Biophys Res Commun. 2010 Mar 19;393(4):800-5. doi: 10.1016/j.bbrc.2010.02.086. Epub 2010 Feb 18.
Vascular endothelial growth factor (Vegf) was previously shown to be expressed specifically in the condylar cartilage of temporomandibular joint-osteoarthritis (TMJ-OA) model rats. Here we demonstrate for the first time that hypoxia-inducible factor-1alpha (Hif-1alpha) is activated in mature chondrocytes of temporomandibular joint-osteoarthritis (TMJ-OA) model rat by mechanical overload, and that activated Hif-1 in chondrocytes can induce osteoclastogenesis via repression of osteoprotegerin (Opg) expression. In rat TMJs, degeneration of the condylar cartilage became prominent in proportion to the duration of overloading. Hif-1alpha expression was observed specifically in mature and hypertrophic chondrocytes, and Hif-1alpha-positivity, level of Vegf expression, and tartrate-resistant acid phosphatase (TRAP)-positive cell numbers all increased in the same manner. When ATDC5 cells induced differentiation by insulin were cultured under hypoxia, Hif-1alpha induction was observed in mature stage, but not in immature stage. Inductions of Hif-1-target genes showed a similar expression pattern. In addition, expression of Opg decreased in hypoxia, and Hif-1alpha played a role, in part, in its regulation.
血管内皮生长因子（Vegf）先前被证明在颞下颌关节骨关节炎（TMJ-OA）模型大鼠的髁状突软骨中特异性表达。在这里，我们首次证明，机械超负荷会激活颞下颌关节骨关节炎（TMJ-OA）模型大鼠成熟软骨细胞中的缺氧诱导因子-1α（Hif-1α），并且软骨细胞中激活的 Hif-1 可以通过抑制护骨素（Opg）的表达来诱导破骨细胞生成。在大鼠 TMJ 中，随着超负荷持续时间的延长，髁状突软骨的退化变得更加明显。Hif-1α 表达特异性出现在成熟和肥大的软骨细胞中，Hif-1α 阳性、Vegf 表达水平和抗酒石酸酸性磷酸酶（TRAP）阳性细胞数量均以相同的方式增加。当用胰岛素诱导 ATDC5 细胞分化并在低氧条件下培养时，在成熟阶段观察到 Hif-1α 的诱导，而在不成熟阶段则没有。Hif-1 靶基因的诱导也表现出相似的表达模式。此外，Opg 的表达在低氧条件下下降，Hif-1α 在其调节中起一定作用。
