Ding Hong, Wei Jianlu, Zhao Yunpeng, Liu Yi, Liu Lian, Cheng Lei
Department of Orthopaedics, Qilu Hospital of Shandong University, Jinan, China.
Oncotarget. 2017 Nov 29;8(65):109692-109702. doi: 10.18632/oncotarget.22766. eCollection 2017 Dec 12.
Atsttrin, an engineered molecule composed of three fragments of progranulin(PGRN), exerts comparable anti-inflammation ability. Intervertebral disc degeneration (IDD) is involved in inflammation in which TNF-α plays a key role. This study aims to examine the effect and the mechanism of Atsttrin in the pathogenesis of intervertebral disc degeneration. For this purpose, we took advantage of murine and human intervertebral disc (IVD) and examined the expression of TNF-α in IVD tissues using immunohistochemistry and TNF-α level in peripheral sera by ELISA assay. Moreover, murine IVD was taken to undergo the Safranin O and HE staining. Furthermore, primary human nucleus pulposus cells were used for immunohistochemistry staining, fluorescent staining, Western Blot, ELISA assay and RT-PCR assay. Herein we found TNF-α expression was elevated in intervertebral disc and peripheral sera in patients with IDD. Interestingly, Atsttrin effectively inhibited TNF-α-mediated catabolism in murine disc by study. TNF-α-induced inflammatory cytokines were strongly reduced in presence of Atsttrin in primary human disc. Mechanism study indicated Atsttrin protected against intervertebral disc degeneration by inhibiting TNF-α-induced inflammation. These findings show that Atsttrin is a potential molecular target for disc degenerative diseases.
Atsttrin是一种由三种颗粒蛋白前体（PGRN）片段组成的工程分子，具有相当的抗炎能力。椎间盘退变（IDD）与炎症有关，其中肿瘤坏死因子-α（TNF-α）起关键作用。本研究旨在探讨Atsttrin在椎间盘退变发病机制中的作用及机制。为此，我们利用小鼠和人类椎间盘（IVD），通过免疫组织化学检测IVD组织中TNF-α的表达，并通过ELISA检测外周血清中TNF-α水平。此外，对小鼠IVD进行番红O和苏木精-伊红染色。此外，原代人髓核细胞用于免疫组织化学染色、荧光染色、蛋白质免疫印迹、ELISA检测和逆转录-聚合酶链反应检测。在此我们发现，IDD患者椎间盘和外周血清中TNF-α表达升高。有趣的是，通过研究发现Atsttrin可有效抑制小鼠椎间盘中TNF-α介导的分解代谢。在原代人椎间盘中，Atsttrin存在时TNF-α诱导的炎性细胞因子大幅减少。机制研究表明，Atsttrin通过抑制TNF-α诱导的炎症来预防椎间盘退变。这些发现表明，Atsttrin是椎间盘退行性疾病的一个潜在分子靶点。
