Oncotarget

Research Papers:

Ghrelin protects against nucleus pulposus degeneration through inhibition of NFκB signaling pathway and activation of Akt signaling pathway

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Oncotarget. 2017; 8:91887-91901. https://doi.org/10.18632/oncotarget.19695

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Weiwei Li1, Xihai Wu2, Ruize Qu3, Wenhan Wang3, Xiaomin Chen3, Lei Cheng4, Yaoge Liu3, Linlin Guo3, Yunpeng Zhao4 and Chao Liu5

1Department of Pathology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P. R. China

2Department of Gynaecology and Obstetrics, Jinan Central Hospital, Shandong University, Jinan, Shandong 250012, P. R. China

3Medical School of Shandong University, Jinan, Shandong 250012, P. R. China

4Department of Orthopaedics, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P. R. China

5Department of Oral and Maxillofacial Surgery and Institute of Dental Medicine, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P. R. China

Correspondence to:

Chao Liu, email: [email protected]

Yunpeng Zhao, email: [email protected]

Keywords: nucleus pulposus, IL-1β, ghrelin, NF-κB signaling, Akt signaling

Received: January 30, 2017     Accepted: June 27, 2017     Published: July 31, 2017

ABSTRACT

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.