Li Weiwei, Wu Xihai, Qu Ruize, Wang Wenhan, Chen Xiaomin, Cheng Lei, Liu Yaoge, Guo Linlin, Zhao Yunpeng, Liu Chao
Department of Pathology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P. R. China.
Department of Gynaecology and Obstetrics, Jinan Central Hospital, Shandong University, Jinan, Shandong 250012, P. R. China.
Oncotarget. 2017 Jul 31;8(54):91887-91901. doi: 10.18632/oncotarget.19695. eCollection 2017 Nov 3.
The objective of the present study was to examine the potential role of ghrelin in degeneration of nucleus pulposus (NP). Lower expression levels of ghrelin were found in human NP cells stimulated with interleukin-1β (IL-1β). Moreover, exogenous ghrelin suppressed IL-1β induced degeneration and inflammation associated biomarkers in human NP cells, including matrix metalloproteinase-13, a disintegrin and metalloproteinase with thrombospondin motifs-5, tumor necrosis factor-α and iNOS, which was possibly mediated by antagonization of NF-κB signaling. Moreover, ghrelin enhanced production of critical extracellular matrix of NP cells, including collagen 2, aggrecan, and Sox-9 in NP cells. Ghrelin also promoted NP tissue regeneration in a rabbit IVD degeneration model, which seems to be associated with growth hormone secretagogue receptor. Additionally, the protective role of ghrelin in anabolism potentially relies on activation of Akt signaling pathway. Taken together, ghrelin may represent a molecular target for prevention and treatment of intervertebral disc degeneration.
本研究的目的是探讨胃饥饿素在髓核（NP）退变中的潜在作用。在用白细胞介素-1β（IL-1β）刺激的人NP细胞中发现胃饥饿素的表达水平较低。此外，外源性胃饥饿素抑制了IL-1β诱导的人NP细胞退变和炎症相关生物标志物，包括基质金属蛋白酶-13、含血小板反应蛋白基序的解聚素和金属蛋白酶-5、肿瘤坏死因子-α和诱导型一氧化氮合酶，这可能是通过拮抗NF-κB信号传导介导的。此外，胃饥饿素增强了NP细胞关键细胞外基质的产生，包括NP细胞中的Ⅱ型胶原、聚集蛋白聚糖和Sox-9。胃饥饿素还促进了兔椎间盘退变模型中NP组织的再生，这似乎与生长激素促分泌素受体有关。此外，胃饥饿素在合成代谢中的保护作用可能依赖于Akt信号通路的激活。综上所述，胃饥饿素可能是预防和治疗椎间盘退变的分子靶点。
