Ghrelin protects against nucleus pulposus degeneration through inhibition of NF-κB signaling pathway and activation of Akt signaling pathway

// Weiwei Li 1 , Xihai Wu 2 , Ruize Qu 3 , Wenhan Wang 3 , Xiaomin Chen 3 , Lei Cheng 4 , Yaoge Liu 3 , Linlin Guo 3 , Yunpeng Zhao 4 and Chao Liu 5 1 Department of Pathology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P. R. China 2 Department of Gynaecology and Obstetrics, Jinan Central Hospital, Shandong University, Jinan, Shandong 250012, P. R. China 3 Medical School of Shandong University, Jinan, Shandong 250012, P. R. China 4 Department of Orthopaedics, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P. R. China 5 Department 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: yishengwwh@163.com Yunpeng Zhao, email: miraculously2008@163.com 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.