Tajika Yutaro, Moue Tatsuya, Ishikawa Shintaro, Asano Kazuhito, Okumo Takayuki, Takagi Hiroshi, Hisamitsu Tadashi
Department of Physiology, School of Medicine, Showa University, Tokyo, Japan.
Department of Physiology, School of Medicine, Showa University, Tokyo, Japan
In Vivo. 2017 Jan 2;31(1):69-77. doi: 10.21873/invivo.11027.
Periostin (POSTN) is a protein that binds to integrins to support adhesion and migration of epithelial cells. Mice lacking this gene exhibit cardiac valve disease as well as skeletal and dental defects. Recent studies indicated that periostin is involved in the pathogenesis and progression of knee osteoarthritis (OA). We investigated the influence of periostin and matrix metalloproteinases (MMPs) on OA synoviocytes.
OA patients were classified according to the Kellgren-Lawrence system and the levels of periostin, interleukin (IL)-4, IL-13 and transforming growth factor-β (TGFβ) in the synovial fluid were measured. MMPs or tissue inhibitor of MMPs (TIMPs) with periostin in cultured cells were measured when periostin was added to OA-associated synovial cells. Dexamethasone, a steroid medication which shows immunosuppressive effects, was used to investigate the influence of the downstream cascade.
Periostin and IL-13 levels were up-regulated during the progression of OA. MMP-2 and MMP-3 levels increased in a periostin concentration-dependent manner. Increase in MMP-2 and MMP-3 levels was inhibited by dexamethasone treatment.
In vivo results herein indicate that IL-13 may induce periostin production in OA. Furthermore, periostin may facilitate MMP production in OA-associated synovial cells.
骨膜蛋白(POSTN)是一种与整合素结合以支持上皮细胞黏附和迁移的蛋白质。缺乏该基因的小鼠表现出心脏瓣膜疾病以及骨骼和牙齿缺陷。最近的研究表明,骨膜蛋白参与膝关节骨关节炎(OA)的发病机制和进展。我们研究了骨膜蛋白和基质金属蛋白酶(MMPs)对OA滑膜细胞的影响。
根据Kellgren-Lawrence系统对OA患者进行分类,并测量滑液中骨膜蛋白、白细胞介素(IL)-4、IL-13和转化生长因子-β(TGFβ)的水平。当将骨膜蛋白添加到OA相关滑膜细胞中时,测量培养细胞中MMPs或MMPs组织抑制剂(TIMPs)与骨膜蛋白的含量。地塞米松是一种具有免疫抑制作用的类固醇药物,用于研究下游级联反应的影响。
在OA进展过程中,骨膜蛋白和IL-13水平上调。MMP-2和MMP-3水平以骨膜蛋白浓度依赖性方式增加。地塞米松治疗可抑制MMP-2和MMP-3水平的升高。
本文的体内结果表明,IL-13可能在OA中诱导骨膜蛋白的产生。此外,骨膜蛋白可能促进OA相关滑膜细胞中MMP的产生。