Pigment Epithelium-Derived Factor (PEDF) mediates cartilage matrix loss in an age-dependent manner under inflammatory conditions.
Pigment Epithelium-Derived Factor (PEDF) mediates cartilage matrix loss in an age-dependent manner under inflammatory conditions.
复制标题
颜料上皮衍生因子（PEDF）在炎症条件下以年龄依赖性方式介导软骨基质损失。
DOI：
10.1186/s12891-017-1410-y
复制
发表时间：
2017-01-25
影响因子：
2.3
通讯作者：
Zeng L
中科院分区：
文献类型：
--
作者：
Nakamura DS;Hollander JM;Uchimura T;Nielsen HC;Zeng L
炎症是软骨破坏的主要原因，并导致关节炎关节代谢活动失衡。据报道，色素上皮衍生因子（PEDF）在各种细胞类型中均具有促炎和抗炎活性，并且在关节炎关节中表达上调，但其在关节破坏中的作用尚不清楚。我们的目的是研究 PEDF 在炎症条件下软骨退化中的作用。 PEDF 在原代人关节软骨细胞中异位表达，并评估了响应促炎细胞因子白细胞介素 1β (IL-1β) 的分解代谢基因表达和蛋白质分泌。 PEDF 缺陷型小鼠和野生型小鼠的跖骨在存在或不存在 IL-1β 的情况下进行培养。评估软骨基质完整性和基质金属蛋白酶 MMP-1、MMP-3 和 MMP-13。在碘乙酸钠 (MIA) 炎症性关节破坏动物模型中对 PEDF 缺陷型和野生型小鼠进行评估，以确定 PEDF 在体内炎症性关节炎中的作用。在适当的情况下，分别对参数数据和非参数数据采用学生 t 检验和曼-惠特尼检验。我们发现，与正常样本相比，人类骨关节炎样本中的 PEDF 蛋白水平较高。我们证明，在 IL-1β 存在的情况下，原代人关节软骨细胞中的异位 PEDF 表达会加剧分解代谢基因的表达。在全骨器官培养中，IL-1β 诱导 MMP-1、MMP-3 和 MMP-13 蛋白产生，并导致显着的软骨基质损失。有趣的是，甲苯胺蓝染色显示，与野生型动物相比，29 周龄动物（而非 10 周龄动物）的 PEDF 缺陷骨骼响应 IL-1β 的基质损失减少。此外，29 周龄动物中缺乏 PEDF 的 MIA 关节破坏模型在体内可保持基质完整性并防止细胞损失。我们得出的结论是，PEDF 在炎症环境下以年龄依赖性方式加剧软骨退化。这是第一项确定 PEDF 在关节炎症中特定作用的研究，并强调了 PEDF 的多方面活性。本文的在线版本 (doi:10.1186/s12891-017-1410-y) 包含补充材料，可供授权用户使用。
Inflammation is a major cause of cartilage destruction and leads to the imbalance of metabolic activities in the arthritic joint. Pigment epithelium-derived factor (PEDF) has been reported to have both pro- and anti-inflammatory activities in various cell types and to be upregulated in the arthritic joint, but its role in joint destruction is unclear. Our aim was to investigate the role of PEDF in cartilage degeneration under inflammatory conditions. PEDF was ectopically expressed in primary human articular chondrocytes, and catabolic gene expression and protein secretion in response to the pro-inflammatory cytokine interleukin 1 beta (IL-1β) were evaluated. Metatarsal bones from PEDF-deficient and wild type mice were cultured in the presence or absence of IL-1β. Cartilage matrix integrity and matrix metalloproteinases MMP-1, MMP-3, and MMP-13 were evaluated. PEDF-deficient and wild type mice were evaluated in the monosodium iodoacetate (MIA) inflammatory joint destruction animal model to determine the role of PEDF in inflammatory arthritis in vivo. Student’s t-tests and Mann–Whitney tests were employed where appropriate, for parametric and non-parametric data, respectively. We showed that PEDF protein levels were higher in human osteoarthritis samples compared to normal samples. We demonstrated that ectopic PEDF expression in primary human articular chondrocytes exacerbated catabolic gene expression in the presence of IL-1β. In whole bone organ cultures, IL-1β induced MMP-1, MMP-3 and MMP-13 protein production, and caused significant cartilage matrix loss. Interestingly, Toluidine Blue staining showed that PEDF-deficient bones from 29 week old animals, but not 10 week old animals, had reduced matrix loss in response to IL-1β compared to their wild type counterparts. In addition, PEDF-deficiency in 29 week old animals preserved matrix integrity and protected against cell loss in the MIA joint destruction model in vivo. We conclude that PEDF exacerbates cartilage degeneration in an age-dependent manner under an inflammatory setting. This is the first study identifying a specific role for PEDF in joint inflammation and highlights the multi-faceted activities of PEDF. The online version of this article (doi:10.1186/s12891-017-1410-y) contains supplementary material, which is available to authorized users.