Roles of hypoxia inducible factor-1α in the temporomandibular joint
Roles of hypoxia inducible factor-1α in the temporomandibular joint
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DOI：
10.1016/j.archoralbio.2016.10.028
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发表时间：
2017-01-01
影响因子：
3
通讯作者：
Tanaka, Eiji
中科院分区：
文献类型：
--
作者：
Mino-Oka, Akiko;Izawa, Takashi;Tanaka, Eiji
目的：颞下颌关节骨关节炎（TMJ-OA）是一种以永久性软骨缺损为特征的退行性疾病。关节软骨保持在低氧环境中。软骨细胞对缺氧条件的反应涉及缺氧诱导因子1 α（HIF-1 α）的表达，其诱导软骨细胞增加血管内皮生长因子（VEGF）的表达。在此，我们研究了机械负荷对杂合HIF-1 α缺陷小鼠（HIF-1 α（+/-））髁突软骨和软骨下骨的影响中HIF-1 α的作用。设计：用滑板对C57 BL/6 NCr野生型（WT）和HIF-1 α（+/-）小鼠的TMJ施加机械应力10天。组织学分析进行了HE染色，番红-O/快速绿色染色，和免疫染色的特定关节软骨homeostasis.Results：HIF-1 α +/-小鼠有较薄的软骨和较小面积的蛋白多糖比WT对照组，没有和机械应力。结论：机械应力条件下，HIF-1 α可能对TMJ关节软骨内环境的稳定和关节软骨的降解具有重要的保护作用，因此HIF-1 α可能成为TMJ-OA治疗的一个重要新靶点。(C)2016爱思唯尔有限公司版权所有
Objective: Temporomandibular joint osteoarthritis (TMJ-OA) is a degenerative disease characterized by permanent cartilage loss. Articular cartilage is maintained in a low-oxygen environment. The chondrocyte response to hypoxic conditions involves expression of hypoxia inducible factor 1 alpha (HIF-1 alpha), which induces chondrocytes to increase expression of vascular endothelial growth factor (VEGF). Here, we investigated the role of HIF-1 alpha in mechanical load effects on condylar cartilage and subchondral bone in heterozygous HIF-1 alpha-deficient mice (HIF-1 alpha(+/-)).Design: Mechanical stress was applied to the TMJ of C57BL/6NCr wild-type (WT) and HIF-1 alpha(+/-) mice with a sliding plate for 10 days. Histological analysis was performed by HE staining, Safranin-O/Fast green staining, and immunostaining specific for articular cartilage homeostasis.Results: HIF-1 alpha+/- mice had thinner cartilage and smaller areas of proteoglycan than WT controls, without and with mechanical stress. Mechanical stress resulted in prominent degenerative changes with increased expression of HIF-1 alpha, VEGF, and the apoptosis factor cleaved Caspase-3 in condylar cartilage.Conclusion: Our results indicate that HIF-1 alpha may be important for articular cartilage homeostasis and protective against articular cartilage degradation in the TMJ under mechanical stress condition, therefore HIF-1 alpha could be an important new therapeutic target in TMJ-OA. (C) 2016 Elsevier Ltd. All rights reserved.