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

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-1? (IL-1?). Moreover, exogenous ghrelin suppressed IL-1? 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-? and iNOS, which was possibly mediated by antagonization of NF-?B 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.

SUBMITTER: Li W

PROVIDER: S-EPMC5696149 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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

Li Weiwei W Wu Xihai X Qu Ruize R Wang Wenhan W Chen Xiaomin X Cheng Lei L Liu Yaoge Y Guo Linlin L Zhao Yunpeng Y Liu Chao C

Oncotarget 20170731 54

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 p ...[more]

PMID: 29190883

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Project description:Background contextLow back pain, affecting nearly 40% of adults, mainly results from intervertebral disc degeneration (IVDD), while the pathogenesis of IVDD is still not fully elucidated. Recently, some researches have revealed that necroptosis, a programmed necrosis, participated in the progression of IVDD, nevertheless, the underlying mechanism remains unclear.PurposeTo study the mechanism of necroptosis of Nucleus Pulposus (NP) cells in IVDD, focusing on the role of MyD88 signaling.Study designThe expression and co-localization of necroptotic indicators and MyD88 were examined in vivo, and MyD88 inhibitor was applied to determine the role of MyD88 signaling in necroptosis of NP cells in vitro.MethodsHuman disc specimens were collected from patients receiving diskectomy for lumbar disc herniation (LDH) or traumatic lumbar fractures after MRI scanning. According to the Pfirrmann grades, they were divided into normal (Grades 1, 2) and degenerated groups (4, 5). Tissue slides were prepared for immunofluorescence to assess the co-localization of necroptotic indicators (RIP3, MLKL, p-MLKL) and MyD88 histologically. The combination of TNFα, LPS and Z-VAD-FMK was applied to induce necroptosis of NP cells. Level of ATP, reactive oxygen species (ROS), live-cell staining and electron microscope study were employed to study the role of MyD88 signaling in necroptosis of NP cells.ResultsIn vivo, the increased expression and co-localization of necroptotic indicators (RIP3, MLKL, p-MLKL) and MyD88 were found in NP cells of degenerated disc, while very l low fluorescence intensity in tissue of traumatic lumbar fractures. In vitro, the MyD88 inhibitor effectively rescued the necroptosis of NP cells, accompanied by increased viability, ATP level, and decreased ROS level. The effect of MyD88 inhibition on necroptosis of NP cells was further confirmed by ultrastructure of mitochondria shown by Transmission Electron Microscope (TEM).ConclusionOur results indicated that the involvement of MyD88 signaling in the necroptosis of NP cells in IVDD, which will replenish the pathogenesis of IVDD and provide a novel potential therapeutic target for IVDD.

Dataset Information

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

Publications

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

Similar Datasets

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