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兰州大学第二医院骨科,甘肃 兰州 730030
刘永,第一作者,研究方向:脊柱外科,E-mail:liuyong1367412623@163.com
纸质出版日期:2024-11-20,
收稿日期:2024-07-04,
录用日期:2024-09-22
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刘永,张海鸿.Sonic Hedgehog信号通路参与椎间盘退变的研究进展[J].中山大学学报(医学科学版),2024,45(06):968-975.
LIU Yong,ZHANG Haihong.Research Progress of Sonic Hedgehog Signaling Pathway Involved in Intervertebral Disc Degeneration[J].Journal of Sun Yat-sen University(Medical Sciences),2024,45(06):968-975.
刘永,张海鸿.Sonic Hedgehog信号通路参与椎间盘退变的研究进展[J].中山大学学报(医学科学版),2024,45(06):968-975. DOI: 10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).20241021.003.
LIU Yong,ZHANG Haihong.Research Progress of Sonic Hedgehog Signaling Pathway Involved in Intervertebral Disc Degeneration[J].Journal of Sun Yat-sen University(Medical Sciences),2024,45(06):968-975. DOI: 10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).20241021.003.
随着社会老龄化的加剧,越来越多的患者受到腰背痛的困扰,给患者和社会带来负担。椎间盘退变(IVDD)是导致慢性腰背痛的主要原因,阐明IVDD的致病机制对解决当前所面临的健康问题具有重要意义。近年来,关于Sonic Hedgehog(Shh)通路在IVDD中的研究报道不断出现,Shh信号通路在椎间盘的形成和出生后维持中具有重要作用,并且该通路的表达变化伴随着椎间盘的年龄相关性退行性改变,靶向Shh信号通路可能在IVDD治疗中具有重要意义。本研究对Shh通路在IVDD中的研究进展进行总结,试图探索该信号通路与IVDD的各种已知病理之间的可能联系,并对未来的研究内容进行展望,以期为探究IVDD的有效治疗方式及预防手段提供参考。
With the intensification of aging society, more and more patients are troubled by low back pain, which brings burden to patients and society. Intervertebral disc degeneration (IVDD) is the main cause of chronic low back pain. Clarifying the pathogenic mechanism of IVDD is of great significance to solve the current health problems. In recent years, there have been a lot of reports on the role of the Sonic Hedgehog (Shh) pathway in IVDD. Shh signaling pathway plays an important role in the formation and postnatal maintenance of intervertebral disc, and the expression change of this pathway is accompanied by age-related degenerative changes of intervertebral disc. Targeting the Shh signaling pathway may have important implications in IVDD treatment. This review summarizes the research progress of Shh signaling pathway in IVDD, attempts to explore the possible relationship between this signaling pathway and various known pathologies of IVDD, and looks forward to future research content, in order to provide reference for exploring effective treatment and prevention methods of IVDD.
椎间盘退变Sonic Hedgehog髓核细胞脊索细胞胶质瘤相关癌基因同源蛋白
intervertebral disc degenerationSonic Hedgehognucleus pulposus cellnotochord cellglioma-associated oncogene homologue
Chou R. Low back pain[J]. Ann Intern Med, 2021, 174(8): Itc113-itc128.
Williams RJ, Tryfonidou MA, Snuggs JW, et al. Cell sources proposed for nucleus pulposus regeneration[J]. JOR Spine, 2021, 4(4): e1175.
Genedy HH, Humbert P, Laoulaou B, et al. MicroRNA-targeting nanomedicines for the treatment of intervertebral disc degeneration[J]. Adv Drug Deliv Rev, 2024, 207: 115214.
Chen X, Zhang A, Zhao K, et al. The role of oxidative stress in intervertebral disc degeneration: mechanisms and therapeutic implications[J]. Ageing Res Rev, 2024, 98: 102323.
Rustenburg CME, Emanuel KS, Peeters M, et al. Osteoarthritis and intervertebral disc degeneration: quite different, quite similar[J]. JOR Spine, 2018, 1(4): e1033.
Chen F, Liu H, Wang X, et al. melatonin activates autophagy via the NF-κB signaling pathway to prevent extracellular matrix degeneration in intervertebral disc[J]. Osteoarthritis Cartilage, 2020, 28(8): 1121-1132.
Yurube T, Hirata H, Ito M, et al. Involvement of autophagy in rat tail static compression-induced intervertebral disc degeneration and notochordal cell disappearance[J]. Int J Mol Sci, 2021, 22(11): 5648.
Giers MB, Munter BT, Eyster KJ, et al. Biomechanical and endplate effects on nutrient transport in the intervertebral disc[J]. World Neurosurg, 2017, 99: 395-402.
Sampara P, Banala RR, Vemuri SK, et al. Understanding the molecular biology of intervertebral disc degeneration and potential gene therapy strategies for regeneration: a review[J]. Gene Ther, 2018, 25(2): 67-82.
谢良玉, 曹盛楠, 李华忠, 等. 剪切力对椎间盘退行性变的影响及其作用机制[J]. 新医学, 2022, 53(6): 395-399.
Xie LY, Cao SN, Li HZ, et al. The effect of shear stress on intervertebral disc degeneration and its mechanism[J]. J New Med, 2022, 53(6): 395-399.
Yurube T, Takeoka Y, Kanda Y, et al. Intervertebral disc cell fate during aging and degeneration: apoptosis, senescence, and autophagy[J]. N Am Spine Soc J, 2023, 14: 100210.
Binch ALA, Fitzgerald JC, Growney EA, et al. Cell-based strategies for IVD repair: clinical progress and translational obstacles[J]. Nat Rev Rheumatol, 2021, 17(3): 158-175.
Mohanty S, Dahia CL. Defects in intervertebral disc and spine during development, degeneration, and pain: New research directions for disc regeneration and therapy[J]. Wiley Interdiscip Rev Dev Biol, 2019, 8(4): e343.
Varjosalo M, Taipale J. Hedgehog: Functions and mechanisms[J]. Genes Dev, 2008, 22(18): 2454-2472.
Teglund S, Toftgård R. Hedgehog beyond medulloblastoma and basal cell carcinoma[J]. Biochim Biophys Acta, 2010, 1805(2): 181-208.
Parashar A, Jha D, Mehta V, et al. Sonic hedgehog signalling pathway contributes in age-related disorders and Alzheimer's disease[J]. Ageing Res Rev, 2024, 96: 102271.
Johnston JJ, Olivos-Glander I, Killoran C, et al. Molecular and clinical analyses of Greig cephalopolysyndactyly and Pallister-Hall syndromes: robust phenotype prediction from the type and position of GLI3 mutations[J]. Am J Hum Genet, 2005, 76(4): 609-622.
Song J, Ge Y, Sun X, et al. Noncoding RNAs related to the hedgehog pathway in cancer: clinical implications and future perspectives[J]. Mol Cancer, 2022, 21(1): 115.
Zhang Y, Beachy PA. Cellular and molecular mechanisms of hedgehog signalling[J]. Nat rev Mol Cell Biol, 2023, 24(9): 668-687.
Rajesh D, Dahia CL. Role of sonic hedgehog signaling pathway in intervertebral disc formation and maintenance[J]. Curr Mol Biol Rep, 2018, 4(4): 173-179.
Ruel L, Thérond PP. Variations in hedgehog signaling: divergence and perpetuation in Sufu regulation of Gli[J]. Genes dev, 2009, 23(16): 1843-1848.
Wang Y, Lu S, Chen Y, et al. Smoothened is a therapeutic target for reducing glutamate toxicity in ischemic stroke[J]. Sci Transl Med, 2021, 13(610): eaba3444.
Wu W, Zhang J, Chen F, et al. Overexpression of CISD2 alleviates septic acute kidney injury via activating sonic hedgehog signaling pathway[J]. Cell Mol Biol (Noisy-le-grand), 2024, 70(5): 238-242.
Hai B, Zhao Q, Deveau MA, et al. Delivery of sonic hedgehog gene repressed irradiation-induced cellular senescence in salivary glands by promoting DNA repair and reducing oxidative stress[J]. Theranostics, 2018, 8(4): 1159-1167.
Berrino C, Omar A. Unravelling the mysteries of the sonic hedgehog pathway in cancer stem cells: activity, crosstalk and regulation[J]. Curr Issues Mol Biol, 2024, 46(6): 5397-5419.
Choi KS, Lee C, Harfe BD. Sonic hedgehog in the notochord is sufficient for patterning of the intervertebral discs[J]. Mech Dev, 2012, 129(9-12): 255-262.
Choi KS, Harfe BD. Hedgehog signaling is required for formation of the notochord sheath and patterning of nuclei pulposi within the intervertebral discs[J]. Proc Natl Acad Sci U S A, 2011, 108(23): 9484-9489.
Dahia CL, Mahoney E, Wylie C. Shh signaling from the nucleus pulposus is required for the postnatal growth and differentiation of the mouse intervertebral disc[J]. PLoS One, 2012, 7(4): e35944.
Winkler T, Mahoney EJ, Sinner D, et al. Wnt signaling activates Shh signaling in early postnatal intervertebral discs, and re-activates Shh signaling in old discs in the mouse[J]. PLoS One, 2014, 9(6): e98444.
Zhang L, Hu S, Xiu C, et al. Intervertebral disc-intrinsic hedgehog signaling maintains disc cell phenotypes and prevents disc degeneration through both cell autonomous and non-autonomous mechanisms[J]. Cell Mol Life Sci, 2024, 81(1): 74.
巩婷婷, 陈建权. Shh/Ihh在小鼠胚胎椎间盘形成过程中的表达[J]. 中国组织工程研究, 2020, 24(32): 5097-5101.
Gong TT, Chen JQ. Expression of Shh/Ihh during intervertebral disc formation in mouse embryos [J]. Tissue Engin Res Chin, 2020, 24(32): 5097-5101.
Peck SH, Mckee KK, Tobias JW, et al. Whole transcriptome analysis of notochord-derived cells during embryonic formation of the nucleus pulposus[J]. Sci Rep, 2017, 7(1): 10504.
Bonavita R, Vincent K, Pinelli R, et al. Formation of the sacrum requires down-regulation of sonic hedgehog signaling in the sacral intervertebral discs[J]. Biol Open, 2018, 7(7): bio035592.
Zhuang Y, Liu L, Liu M, et al. The sonic hedgehog pathway suppresses oxidative stress and senescence in nucleus pulposus cells to alleviate intervertebral disc degeneration via GPX4[J]. Biochim Biophys Acta Mol Basis Dis, 2024, 1870(2): 166961.
Mohanty S, Pinelli R, Pricop P, et al. Chondrocyte-like nested cells in the aged intervertebral disc are late-stage nucleus pulposus cells[J]. Aging Cell, 2019, 18(5): e13006.
Liu L, Zhang Y, Fu J, et al. Gli1 depletion induces oxidative stress and apoptosis of nucleus pulposus cells via Fos in intervertebral disc degeneration[J]. J Orthop Translat, 2023, 40: 116-131.
Chen R, Tan Y, Li Y, et al. Exogenous indian hedgehog antagonist damages intervertebral discs homeostasis in adult mice[J]. J Orthop Translat, 2022, 36: 164-176.
Li X, Yang S, Han L, et al. Ciliary IFT80 is essential for intervertebral disc development and maintenance[J]. Faseb j, 2020, 34(5): 6741-6756.
Ding Q, Ren Y, Che H, et al. Cyclooxygenase-2 deficiency causes delayed ossification of lumbar vertebral endplates[J]. Am J Transl Res, 2018, 10(3): 718-730.
Li Y, Wei Y, Li H, et al. Exogenous parathyroid hormone alleviates intervertebral disc degeneration through the sonic hedgehog signalling pathway mediated by CREB[J]. Oxid Med Cell Longev, 2022, 2022: 9955677.
Zhang Y, Wang Y, Zhou X, et al. Osmolarity controls the differentiation of adipose-derived stem cells into nucleus pulposus cells via histone demethylase KDM4B[J]. Mol Cell Biochem, 2020, 472(1-2): 157-171.
Zhou X, Tao Y, Chen E, et al. Genipin-cross-linked type Ⅱ collagen scaffold promotes the differentiation of adipose-derived stem cells into nucleus pulposus-like cells[J]. J Biomed Mater Res A, 2018, 106(5): 1258-1268.
Bach FC, De Rooij KM, Riemers FM, et al. Hedgehog proteins and parathyroid hormone-related protein are involved in intervertebral disc maturation, degeneration, and calcification[J]. JOR Spine, 2019, 2(4): e1071.
Bao J, Qian Z, Liu L, et al. Pharmacological disruption of phosphorylated eukaryotic initiation factor-2α/activating transcription factor 4/ Indian hedgehog protects intervertebral disc degeneration via reducing the reactive oxygen species and apoptosis of nucleus pulposus cells[J]. Front Cell Dev Biol, 2021, 9: 675486.
Wang S, Yang K, Chen S, et al. Indian hedgehog contributes to human cartilage endplate degeneration[J]. Eur Spine J, 2015, 24(8): 1720-1728.
Carpenter RL, Ray H. Safety and tolerability of sonic hedgehog pathway inhibitors in cancer[J]. Drug Saf, 2019, 42(2): 263-279.
He J, Sheng T, Stelter AA, et al. Suppressing Wnt signaling by the hedgehog pathway through sFRP-1[J]. J Biol Chem, 2006, 281(47): 35598-35602.
Maeda O, Kondo M, Fujita T, et al. Enhancement of Gli1-transcriptional activity by beta-catenin in human cancer cells[J]. Oncol Rep, 2006, 16(1): 91-96.
Dennler S, André J, Alexaki I, et al. Induction of sonic hedgehog mediators by transforming growth factor-beta: Smad3-dependent activation of Gli2 and Gli1 expression in vitro and in vivo[J]. Cancer Res, 2007, 67(14): 6981-6986.
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