Necroptosis of nucleus pulposus cells involved in intervertebral disc degeneration through MyD88 signaling
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...
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2022.994307/full |
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| author | Hong Fan Hong Fan Zhe Chen Hai-Bin Tang Le-Qun Shan Zi-Yi Chen Shi-Chang Liu Yong-Yuan Zhang Xin-Yu Guo Hao Yang Ding-Jun Hao |
| author_facet | Hong Fan Hong Fan Zhe Chen Hai-Bin Tang Le-Qun Shan Zi-Yi Chen Shi-Chang Liu Yong-Yuan Zhang Xin-Yu Guo Hao Yang Ding-Jun Hao |
| author_sort | Hong Fan |
| collection | DOAJ |
| 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. |
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| language | English |
| last_indexed | 2024-04-12T22:32:20Z |
| publishDate | 2022-09-01 |
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| series | Frontiers in Endocrinology |
| spelling | doaj.art-fd31a3000f6d437f91c3601e3fc7ab3a2022-12-22T03:13:56ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922022-09-011310.3389/fendo.2022.994307994307Necroptosis of nucleus pulposus cells involved in intervertebral disc degeneration through MyD88 signalingHong Fan0Hong Fan1Zhe Chen2Hai-Bin Tang3Le-Qun Shan4Zi-Yi Chen5Shi-Chang Liu6Yong-Yuan Zhang7Xin-Yu Guo8Hao Yang9Ding-Jun Hao10Shaanxi Spine Medicine Research Center, Translational Medicine Center, Department of Spine Surgery, Hong Hui Hospital, Xi’an Jiaotong University, Xi’an, ChinaDepartment of Neurology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaShaanxi Spine Medicine Research Center, Translational Medicine Center, Department of Spine Surgery, Hong Hui Hospital, Xi’an Jiaotong University, Xi’an, ChinaDepartment of Laboratory Medicine, Xi’an Central Hospital, Xi’an Jiaotong University, Xi’an, ChinaShaanxi Spine Medicine Research Center, Translational Medicine Center, Department of Spine Surgery, Hong Hui Hospital, Xi’an Jiaotong University, Xi’an, ChinaDepartment of Endocrinology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaShaanxi Spine Medicine Research Center, Translational Medicine Center, Department of Spine Surgery, Hong Hui Hospital, Xi’an Jiaotong University, Xi’an, ChinaShaanxi Spine Medicine Research Center, Translational Medicine Center, Department of Spine Surgery, Hong Hui Hospital, Xi’an Jiaotong University, Xi’an, ChinaShaanxi Spine Medicine Research Center, Translational Medicine Center, Department of Spine Surgery, Hong Hui Hospital, Xi’an Jiaotong University, Xi’an, ChinaShaanxi Spine Medicine Research Center, Translational Medicine Center, Department of Spine Surgery, Hong Hui Hospital, Xi’an Jiaotong University, Xi’an, ChinaShaanxi Spine Medicine Research Center, Translational Medicine Center, Department of Spine Surgery, Hong Hui Hospital, Xi’an Jiaotong University, Xi’an, ChinaBackground 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.https://www.frontiersin.org/articles/10.3389/fendo.2022.994307/fullivddnecroptosisnucleus pulposus cellsMyD88 signalinglow back pain |
| spellingShingle | Hong Fan Hong Fan Zhe Chen Hai-Bin Tang Le-Qun Shan Zi-Yi Chen Shi-Chang Liu Yong-Yuan Zhang Xin-Yu Guo Hao Yang Ding-Jun Hao Necroptosis of nucleus pulposus cells involved in intervertebral disc degeneration through MyD88 signaling Frontiers in Endocrinology ivdd necroptosis nucleus pulposus cells MyD88 signaling low back pain |
| title | Necroptosis of nucleus pulposus cells involved in intervertebral disc degeneration through MyD88 signaling |
| title_full | Necroptosis of nucleus pulposus cells involved in intervertebral disc degeneration through MyD88 signaling |
| title_fullStr | Necroptosis of nucleus pulposus cells involved in intervertebral disc degeneration through MyD88 signaling |
| title_full_unstemmed | Necroptosis of nucleus pulposus cells involved in intervertebral disc degeneration through MyD88 signaling |
| title_short | Necroptosis of nucleus pulposus cells involved in intervertebral disc degeneration through MyD88 signaling |
| title_sort | necroptosis of nucleus pulposus cells involved in intervertebral disc degeneration through myd88 signaling |
| topic | ivdd necroptosis nucleus pulposus cells MyD88 signaling low back pain |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2022.994307/full |
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