CCN1 Promotes VEGF Production in Osteoblasts and Induces Endothelial Progenitor Cell Angiogenesis by Inhibiting miR-126 Expression in Rheumatoid Arthritis
CCN1 Promotes VEGF Production in Osteoblasts and Induces Endothelial Progenitor Cell Angiogenesis by Inhibiting miR-126 Expression in Rheumatoid Arthritis
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DOI：
10.1002/jbmr.2926
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发表时间：
2017-01-01
影响因子：
6.2
通讯作者：
Tang, Chih-Hsin
中科院分区：
文献类型：
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作者：
Chen, Cheng-Yu;Su, Chen-Ming;Tang, Chih-Hsin
血管生成是从先前存在的脉管系统形成新的毛细血管。血管生成的持续存在在包括类风湿性关节炎（RA）在内的各种疾病的发病机制中发挥着关键作用。富含半胱氨酸 61（Cyr61 或 CCN1）是 RA 中重要的促炎细胞因子。在这里，我们研究了 CCN1 在与血管内皮生长因子 (VEGF) 产生和成骨细胞相关的血管生成中的作用。我们发现与健康对照相比，RA 患者滑液中 CCN1 和 VEGF 的表达更高。 CCN1 通过蛋白激酶 C-α (PKC-) 信号通路抑制 miR-126，诱导成骨细胞中 VEGF 表达并增加内皮祖细胞 (EPC) 血管生成。 CCN1 敲低可抑制体外和体内模型中的血管生成。使用表达短发夹 RNA (shRNA) 的慢病毒载体抑制 CCN1 表达可改善胶原诱导性关节炎 (CIA) 小鼠踝关节的关节肿胀、软骨侵蚀和血管生成。我们的研究首次描述了 CCN1 如何促进成骨细胞中 VEGF 的表达并增加 RA 疾病中 EPC 的血管生成。 CCN1 可能作为 RA 治疗的潜在靶点。 (c) 2016 年美国骨与矿物质研究学会。
Angiogenesis is the formation of new capillaries from preexisting vasculature. The perpetuation of angiogenesis plays a critical role in the pathogenesis of various disease states including rheumatoid arthritis (RA). Cysteine-rich 61 (Cyr61 or CCN1) is an important proinflammatory cytokine in RA. Here, we investigated the role of CCN1 in angiogenesis associated with vascular endothelial growth factor (VEGF) production and osteoblasts. We found higher expression of CCN1 and VEGF in synovial fluid from RA patients compared with healthy controls. CCN1 induced VEGF expression in osteoblasts and increased endothelial progenitor cells (EPCs) angiogenesis by inhibiting miR-126 via the protein kinase C-alpha (PKC-) signaling pathway. CCN1 knockdown inhibited angiogenesis in both in vitro and in vivo models. Inhibition of CCN1 expression with lentiviral vectors expressing short hairpin RNA (shRNA) ameliorated articular swelling, cartilage erosion, and angiogenesis in the ankle joint of mice with collagen-induced arthritis (CIA). Our study is the first to describe how CCN1 promotes VEGF expression in osteoblasts and increased EPCs angiogenesis in RA disease. CCN1 may serve as a potential target for RA treatment. (c) 2016 American Society for Bone and Mineral Research.