Department of Orthopaedics, Qilu Hospital of Shandong University, No.107, Wen Hua Xi Road, Jinan, Shandong, 250012, People's Republic of China.
School of Medicine, Shandong University, Jinan, China.
Inflammation. 2018 Oct;41(5):1852-1863. doi: 10.1007/s10753-018-0828-1.
Progranulin (PGRN) is a widely expressed growth factor that effectively inhibits tumor necrosis factor α (TNFα)-mediated inflammatory response. TNFα is involved in intervertebral disc degeneration (IDD) and plays a key role. This study aims to determine the role of PGRN in the intervertebral disc degeneration process. We collected intervertebral discs (IVDs) from humans and mice with different genetic backgrounds. We examined the expression of PGRN in IVD tissues by immunohistochemistry staining and Western blotting assay. We examined the peripheral serum level of PGRN by ELISA assay. Murine IVD tissue samples were taken to undergo safranin O, HE, and immunohistochemistry staining. Primary human nucleus pulposus cells were used for ELISA and RT-PCR assays. PGRN as well as interlukin-10 (IL-10) and interlukin-17 (IL-17) expressions were elevated in degenerative discs and peripheral blood sera. Loss of PGRN led to accelerated disc degeneration in the animal model, along with decreased expression of IL-10 and increased expression of IL-17. Additionally, the PGRN level was positively related to levels of IL-10 and IL-17. In vitro study suggested that PGRN protected against disc degeneration by inducing IL-10 and reducing IL-17. PGRN is associated with intervertebral disc degeneration through interfering with IL-10 and IL-17; thus, PGRN could be an interesting biomarker for diagnosis and a potential treatment target.
颗粒体蛋白聚糖 (PGRN) 是一种广泛表达的生长因子，能有效抑制肿瘤坏死因子 α (TNFα) 介导的炎症反应。TNFα 参与椎间盘退行性变 (IDD)，并发挥关键作用。本研究旨在探讨 PGRN 在椎间盘退行性变过程中的作用。我们收集了不同遗传背景的人类和小鼠的椎间盘组织。通过免疫组织化学染色和 Western blot 检测，检测了 PGRN 在椎间盘组织中的表达。通过 ELISA 检测外周血清中 PGRN 的水平。对小鼠椎间盘组织样本进行番红 O、HE 和免疫组织化学染色。原代人髓核细胞进行 ELISA 和 RT-PCR 检测。退变椎间盘和外周血血清中 PGRN 以及白细胞介素 10 (IL-10) 和白细胞介素 17 (IL-17) 的表达均升高。PGRN 缺失导致动物模型中椎间盘退变加速，同时 IL-10 表达降低，IL-17 表达升高。此外，PGRN 水平与 IL-10 和 IL-17 水平呈正相关。体外研究表明，PGRN 通过诱导 IL-10 和减少 IL-17 来保护椎间盘免受退变。PGRN 通过干扰 IL-10 和 IL-17 与椎间盘退行性变相关；因此，PGRN 可能是一种有前途的诊断生物标志物和潜在的治疗靶点。
