{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,13]],"date-time":"2026-11-13T05:32:12Z","timestamp":1794547932868,"version":"4.9.1"},"reference-count":65,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,11,28]],"date-time":"2018-11-28T00:00:00Z","timestamp":1543363200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2018,11,28]],"date-time":"2018-11-28T00:00:00Z","timestamp":1543363200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Understanding the molecular mechanisms regulating the maintenance and destruction of intervertebral disc may lead to the development of new therapies for intervertebral disc degeneration (IDD). Here we present evidence from miRNA microarray analyses of clinical data sets along with in vitro and in vivo experiments that miR-141 is a key regulator of IDD. Gain- and loss-of-function studies show that miR-141 drives IDD by inducing nucleus pulposus (NP) apoptosis. Furthermore, miR-141 KO in mice attenuated spontaneous and surgically induced IDD. Mechanistically, miR-141 promotes IDD development by targeting and depleting SIRT1, a negative regulator of NF-\u03baB pathway. Therapeutically, upregulation or downregulation of miR-141 by nanoparticle delivery in IDD model aggravated or alleviated experimental IDD, respectively. Our findings reveal a novel mechanism by which miR-141, in part, promotes IDD progression by interacting with SIRT1\/NF-\u03baB pathway. Blockade of miR-141 in vivo may serve as a potential therapeutic approach in the treatment of IDD.<\/jats:p>","DOI":"10.1038\/s41467-018-07360-1","type":"journal-article","created":{"date-parts":[[2018,11,22]],"date-time":"2018-11-22T12:37:32Z","timestamp":1542890252000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":235,"title":["Preclinical development of a microRNA-based therapy for intervertebral disc degeneration"],"prefix":"10.1038","volume":"9","author":[{"given":"Ming-liang","family":"Ji","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue-jun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei-liang","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-tao","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun-tao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,11,28]]},"reference":[{"key":"7360_CR1","doi-asserted-by":"publisher","first-page":"1211","DOI":"10.1016\/S0140-6736(17)32154-2","volume":"390","author":"AA Abajobir","year":"2017","unstructured":"Abajobir, A. A. et al. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet 390, 1211\u20131259 (2017).","journal-title":"Lancet"},{"key":"7360_CR2","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1016\/S0140-6736(15)60692-4","volume":"386","author":"T Vos","year":"2015","unstructured":"Vos, T. et al. Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990\u20132013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 386, 743\u2013800 (2015).","journal-title":"Lancet"},{"issue":"S2","key":"7360_CR3","first-page":"10","volume":"88","author":"S Roberts","year":"2006","unstructured":"Roberts, S. et al. Histology and pathology of the human intervertebral disc. J. Bone Joint Surg. Am. 88(S2), 10\u201314 (2006).","journal-title":"J. Bone Joint Surg. Am."},{"key":"7360_CR4","doi-asserted-by":"publisher","first-page":"832","DOI":"10.1002\/art.37819","volume":"65","author":"J Wang","year":"2013","unstructured":"Wang, J. et al. TNF-\u03b1 and IL-1\u03b2 dependent induction of CCL3 expression by nucleus pulposus cells promotes macrophage migration through CCR1. Arthritis Rheum. 65, 832\u2013842 (2013).","journal-title":"Arthritis Rheum."},{"key":"7360_CR5","doi-asserted-by":"publisher","first-page":"600","DOI":"10.1093\/rheumatology\/ket303","volume":"53","author":"F Lv","year":"2014","unstructured":"Lv, F. et al. In search of nucleus pulposus-specific molecular markers. Rheumatology (Oxf.) 53, 600\u2013610 (2014).","journal-title":"Rheumatology (Oxf.)"},{"key":"7360_CR6","doi-asserted-by":"publisher","first-page":"E178","DOI":"10.1097\/BRS.0b013e3181908ab3","volume":"34","author":"B Peng","year":"2009","unstructured":"Peng, B. et al. Expression and role of connective tissue growth factor in painful disc fibrosis and degeneration. Spine (Phila. Pa 1976) 34, E178\u2013E182 (2009).","journal-title":"Spine (Phila. Pa 1976)"},{"key":"7360_CR7","doi-asserted-by":"publisher","first-page":"2679","DOI":"10.1097\/01.brs.0000146457.83240.eb","volume":"29","author":"MC Battie","year":"2004","unstructured":"Battie, M. C. et al. Lumbar disc degeneration: epidemiology and genetic influences. Spine (Phila. Pa 1976) 29, 2679\u20132690 (2004).","journal-title":"Spine (Phila. Pa 1976)"},{"key":"7360_CR8","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12503","volume":"7","author":"R Nakamichi","year":"2016","unstructured":"Nakamichi, R. et al. Mohawk promotes the maintenance and regeneration of the outer annulus fibrosus of intervertebral discs. Nat. Commun. 7, 12503 (2016).","journal-title":"Nat. Commun."},{"key":"7360_CR9","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1002\/path.1050","volume":"196","author":"AJ Freemont","year":"2002","unstructured":"Freemont, A. J. et al. Current understanding of cellular and molecular events in intervertebral disc degeneration: implications for therapy. J. Pathol. 196, 374\u2013379 (2002).","journal-title":"J. Pathol."},{"key":"7360_CR10","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1007\/s00109-015-1371-2","volume":"94","author":"ML Ji","year":"2016","unstructured":"Ji, M. L. et al. Downregulation of microRNA-193a-3p is involved in intervertebral disc degeneration by targeting MMP14. J. Mol. Med. (Berl.) 94, 457\u2013568 (2016).","journal-title":"J. Mol. Med. (Berl.)"},{"key":"7360_CR11","doi-asserted-by":"publisher","first-page":"4909","DOI":"10.1172\/JCI69277","volume":"123","author":"YQ Song","year":"2013","unstructured":"Song, Y. Q. et al. Lumbar disc degeneration is linked to a carbohydrate sulfotransferase 3 variant. J. Clin. Invest. 123, 4909\u20134917 (2013).","journal-title":"J. Clin. Invest."},{"key":"7360_CR12","doi-asserted-by":"publisher","first-page":"900","DOI":"10.1002\/jbmr.2753","volume":"31","author":"ML Ji","year":"2016","unstructured":"Ji, M. L. et al. Dysregulated miR-98 contributes to extracellular matrix degradation by targeting IL-6\/STAT3 signaling pathway in human intervertebral disc degeneration. J. Bone Miner. Res. 31, 900\u2013909 (2016).","journal-title":"J. Bone Miner. Res."},{"key":"7360_CR13","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/j.cell.2009.01.002","volume":"136","author":"DP Bartel","year":"2009","unstructured":"Bartel, D. P. MicroRNAs: target recognition and regulatory functions. Cell 136, 215\u2013233 (2009).","journal-title":"Cell"},{"key":"7360_CR14","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1038\/nrd.2016.246","volume":"16","author":"R Rupaimoole","year":"2017","unstructured":"Rupaimoole, R. et al. MicroRNA therapeutics: towards a new era for the management of cancer and other diseases. Nat. Rev. Drug Discov. 16, 203\u2013222 (2017).","journal-title":"Nat. Rev. Drug Discov."},{"key":"7360_CR15","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1172\/JCI84424","volume":"127","author":"BD Adams","year":"2017","unstructured":"Adams, B. D. et al. Targeting noncoding RNAs in disease. J. Clin. Invest. 127, 761\u2013771 (2017).","journal-title":"J. Clin. Invest."},{"key":"7360_CR16","doi-asserted-by":"publisher","first-page":"2369","DOI":"10.1038\/sj.emboj.7600244","volume":"23","author":"F Yeung","year":"2004","unstructured":"Yeung, F. et al. Modulation of NF-\u03baB-dependent transcription and cell survival by the SIRT1 deacetylase. EMBO J. 23, 2369\u20132380 (2004).","journal-title":"EMBO J."},{"issue":"9","key":"7360_CR17","doi-asserted-by":"publisher","first-page":"e46364","DOI":"10.1371\/journal.pone.0046364","volume":"7","author":"Hongying Yang","year":"2012","unstructured":"Yang, H. et al. SIRT1 activators suppress inflammatory responses through promotion of p65 deacetylation and inhibition of NF-\u03baB activity. PLoS ONE 7, e46364 (2012).","journal-title":"PLoS ONE"},{"key":"7360_CR18","doi-asserted-by":"publisher","first-page":"1627","DOI":"10.1038\/nm.2512","volume":"17","author":"B Mateescu","year":"2011","unstructured":"Mateescu, B. et al. miR-141 and miR-200a act on ovarian tumorigenesis by controlling oxidative stress response. Nat. Med. 17, 1627\u20131635 (2011).","journal-title":"Nat. Med."},{"key":"7360_CR19","doi-asserted-by":"publisher","first-page":"1247","DOI":"10.1136\/gutjnl-2012-304213","volume":"63","author":"Z Huang","year":"2014","unstructured":"Huang, Z. et al. miR-141 regulates colonic leukocytic trafficking by targeting CXCL12\u03b2 during murine colitis and human Crohn\u2019s disease. Gut 63, 1247\u20131257 (2014).","journal-title":"Gut"},{"key":"7360_CR20","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14270","volume":"8","author":"C Liu","year":"2017","unstructured":"Liu, C. et al. MicroRNA-141 suppresses prostate cancer stem cells and metastasis by targeting a cohort of pro-metastasis genes. Nat. Commun. 8, 14270 (2017).","journal-title":"Nat. Commun."},{"key":"7360_CR21","first-page":"108","volume":"13","author":"BG Debeb","year":"2016","unstructured":"Debeb, B. G. et al. miR-141-mediated regulation of brain metastasis from breast cancer. J. Natl. Cancer Inst. 13, 108\u2013115 (2016).","journal-title":"J. Natl. Cancer Inst."},{"key":"7360_CR22","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1038\/ncb1722","volume":"10","author":"PA Gregory","year":"2008","unstructured":"Gregory, P. A. et al. The mir-200 family and mir-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat. Cell Biol. 10, 593\u2013601 (2008).","journal-title":"Nat. Cell Biol."},{"key":"7360_CR23","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1002\/jor.23628","volume":"36","author":"MH Hu","year":"2018","unstructured":"Hu, M. H. et al. Optimization of puncture injury to rat caudal disc for mimicking early degeneration of intervertebral disc. J. Orthop. Res. 36, 202\u2013211 (2018).","journal-title":"J. Orthop. Res."},{"key":"7360_CR24","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1097\/BRS.0b013e318166e0a2","volume":"33","author":"DM Elliott","year":"2008","unstructured":"Elliott, D. M. et al. The effect of relative needle diameter in puncture and sham injection animal models of degeneration. Spine (Phila. Pa 1976). 33, 588\u2013596 (2008).","journal-title":"Spine (Phila. Pa 1976)."},{"key":"7360_CR25","doi-asserted-by":"publisher","first-page":"2338","DOI":"10.1097\/01.BRS.0000096943.27853.BC","volume":"28","author":"D Anderson","year":"2003","unstructured":"Anderson, D. et al. A fibronectin fragment stimulates intervertebral disc degeneration in vivo. Spine 28, 2338\u20132345 (2003).","journal-title":"Spine"},{"key":"7360_CR26","doi-asserted-by":"publisher","first-page":"1906","DOI":"10.1002\/jor.20221","volume":"24","author":"JI Boxberger","year":"2006","unstructured":"Boxberger, J. I. et al. Nucleus pulposus glycosaminoglycan content is correlated with axial mechanics in rat lumbar motion segments. J. Orthop. Res. 24, 1906\u20131915 (2006).","journal-title":"J. Orthop. Res."},{"key":"7360_CR27","doi-asserted-by":"publisher","first-page":"S86","DOI":"10.1097\/01.BRS.0000104576.37837.89","volume":"28","author":"HS An","year":"2003","unstructured":"An, H. S. et al. Biological repair of intervertebral disc. Spine (Phila. Pa 1976) 28, S86\u2013S92 (2003).","journal-title":"Spine (Phila. Pa 1976)"},{"key":"7360_CR28","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1097\/BRS.0b013e31816054f8","volume":"33","author":"JI Boxberger","year":"2008","unstructured":"Boxberger, J. I. et al. An in vivo model of reduced nucleus pulposus glycosaminoglycan content in the rat lumbar intervertebral disc. Spine (Phila. Pa 1976) 33, 146\u2013154 (2008).","journal-title":"Spine (Phila. Pa 1976)"},{"key":"7360_CR29","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1016\/j.actbio.2017.09.015","volume":"63","author":"C Vergari","year":"2017","unstructured":"Vergari, C. et al. The effects of needle damage on annulus fibrosus micromechanics. Acta Biomater. 63, 274\u2013282 (2017).","journal-title":"Acta Biomater."},{"key":"7360_CR30","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1007\/s10439-005-9070-8","volume":"34","author":"W Johannessen","year":"2006","unstructured":"Johannessen, W. et al. Trans-endplate nucleotomy increases deformation and creep response in axial loading. Ann. Biomed. Eng. 34, 687\u2013696 (2006).","journal-title":"Ann. Biomed. Eng."},{"key":"7360_CR31","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1002\/emmm.201100209","volume":"4","author":"MV Iorio","year":"2012","unstructured":"Iorio, M. V. et al. MicroRNA dysregulation in cancer: diagnostics, monitoring and therapeutics. A comprehensive review. EMBO Mol. Med. 4, 143\u2013159 (2012).","journal-title":"EMBO Mol. Med."},{"key":"7360_CR32","doi-asserted-by":"publisher","first-page":"E757","DOI":"10.1097\/BRS.0000000000001954","volume":"42","author":"J Guo","year":"2017","unstructured":"Guo, J. et al. Role of Sirt1 plays in nucleus pulposus cells and intervertebral disc degeneration. Spine (Phila. Pa 1976) 42, E757\u2013E766 (2017).","journal-title":"Spine (Phila. Pa 1976)"},{"key":"7360_CR33","doi-asserted-by":"publisher","first-page":"E515","DOI":"10.1097\/BRS.0000000000000817","volume":"40","author":"X Xia","year":"2015","unstructured":"Xia, X. et al. SIRT1 plays a protective role in intervertebral disc degeneration in a puncture-induced rodent model. Spine (Phila. Pa 1976) 40, E515\u2013E524 (2015).","journal-title":"Spine (Phila. Pa 1976)"},{"key":"7360_CR34","doi-asserted-by":"publisher","DOI":"10.1038\/srep07456","volume":"4","author":"W Jiang","year":"2014","unstructured":"Jiang, W. et al. SIRT1 protects against apoptosis by promoting autophagy in degenerative human disc nucleus pulposus cells. Sci. Rep. 4, 7456 (2014).","journal-title":"Sci. Rep."},{"key":"7360_CR35","doi-asserted-by":"publisher","first-page":"1397","DOI":"10.1136\/annrheumdis-2012-202620","volume":"73","author":"T Matsuzaki","year":"2017","unstructured":"Matsuzaki, T. et al. Disruption of Sirt1 in chondrocytes causes accelerated progression of osteoarthritis under mechanical stress and during ageing in mice. Ann. Rheum. Dis. 73, 1397\u20131404 (2017).","journal-title":"Ann. Rheum. Dis."},{"key":"7360_CR36","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms15889","volume":"8","author":"S Monteagudo","year":"2017","unstructured":"Monteagudo, S. et al. DOT1L safeguards cartilage homeostasis and protects against osteoarthritis. Nat. Commun. 8, 15889 (2017).","journal-title":"Nat. Commun."},{"key":"7360_CR37","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1136\/ard.2011.200504","volume":"71","author":"O Gabay.","year":"2012","unstructured":"Gabay., O. et al. Increased apoptotic chondrocytes in articular cartilage from adult heterozygous SirT1 mice. Ann. Rheum. Dis. 71, 613\u2013616 (2012).","journal-title":"Ann. Rheum. Dis."},{"key":"7360_CR38","doi-asserted-by":"publisher","first-page":"2731","DOI":"10.1002\/art.24864","volume":"60","author":"K Takayama","year":"2009","unstructured":"Takayama, K. et al. SIRT1 regulation of apoptosis of human chondrocytes. Arthritis Rheum. 60, 2731\u20132740 (2009).","journal-title":"Arthritis Rheum."},{"key":"7360_CR39","doi-asserted-by":"publisher","first-page":"2363","DOI":"10.1002\/art.30279","volume":"63","author":"M Dvir-Ginzberg","year":"2011","unstructured":"Dvir-Ginzberg, M. et al. Tumor necrosis factor \u03b1-mediated cleavage and inactivation of SirT1 in human osteoarthritic chondrocytes. Arthritis Rheum. 63, 2363\u20132373 (2011).","journal-title":"Arthritis Rheum."},{"key":"7360_CR40","doi-asserted-by":"publisher","first-page":"1383","DOI":"10.1002\/art.27369","volume":"62","author":"V Gagarina","year":"2010","unstructured":"Gagarina, V. et al. SirT1 enhances survival of human osteoarthritic chondrocytes by repressing protein tyrosine phosphatase 1B and activating the insulin-like growth factor receptor pathway. Arthritis Rheum. 62, 1383\u20131392 (2010).","journal-title":"Arthritis Rheum."},{"key":"7360_CR41","doi-asserted-by":"publisher","first-page":"1939","DOI":"10.1016\/j.cellsig.2013.06.007","volume":"25","author":"A Kauppinen","year":"2013","unstructured":"Kauppinen, A. et al. Antagonistic crosstalk between NF-\u03baB and SIRT1 in the regulation of inflammation and metabolic disorders. Cell. Signal. 25, 1939\u20131948 (2013).","journal-title":"Cell. Signal."},{"key":"7360_CR42","doi-asserted-by":"publisher","first-page":"ra106","DOI":"10.1126\/scisignal.2005375","volume":"7","author":"S Shinozaki","year":"2014","unstructured":"Shinozaki, S. et al. Inflammatory stimuli induce inhibitory S-nitrosylation of the deacetylase SIRT1 to increase acetylation and activation of p53 and p65. Sci. Signal. 7, ra106 (2014).","journal-title":"Sci. Signal."},{"key":"7360_CR43","doi-asserted-by":"publisher","first-page":"22048","DOI":"10.1074\/jbc.M114.568790","volume":"289","author":"C Buhrmann","year":"2014","unstructured":"Buhrmann, C. et al. Sirtuin-1 (SIRT1) is required for promoting chondrogenic differentiation of mesenchymal stem cells. J. Biol. Chem. 289, 22048\u201322062 (2014).","journal-title":"J. Biol. Chem."},{"key":"7360_CR44","doi-asserted-by":"publisher","first-page":"960","DOI":"10.1002\/jbmr.1824","volume":"28","author":"JR Edwards","year":"2013","unstructured":"Edwards, J. R. et al. Silent information regulator (Sir)T1 inhibits NF-\u03baB signaling to maintain normal skeletal remodeling. J. Bone Miner. Res. 28, 960\u2013969 (2013).","journal-title":"J. Bone Miner. Res."},{"key":"7360_CR45","doi-asserted-by":"publisher","first-page":"11492","DOI":"10.1074\/jbc.M110.198713","volume":"286","author":"M Shakibaei","year":"2011","unstructured":"Shakibaei, M. et al. Resveratrol-mediated SIRT-1 interactions with p300 modulate receptor activator of NF-kappaB ligand (RANKL) activation of NF-kappaB signaling and inhibit osteoclastogenesis in bone-derived cells. J. Biol. Chem. 286, 11492\u201311505 (2011).","journal-title":"J. Biol. Chem."},{"key":"7360_CR46","doi-asserted-by":"publisher","first-page":"25770","DOI":"10.1074\/jbc.M112.355420","volume":"287","author":"F Busch","year":"2012","unstructured":"Busch, F. et al. Sirt-1 is required for the inhibition of apoptosis and inflammatory responses in human tenocytes. J. Biol. Chem. 287, 25770\u201325781 (2012).","journal-title":"J. Biol. Chem."},{"key":"7360_CR47","doi-asserted-by":"publisher","first-page":"38050","DOI":"10.1074\/jbc.M112.377028","volume":"287","author":"F Busch","year":"2012","unstructured":"Busch, F. et al. Resveratrol modulates interleukin-1\u03b2-induced phosphatidylinositol 3-kinase and nuclear factor \u03baB signaling pathways in human tenocytes. J. Biol. Chem. 287, 38050\u201338063 (2012).","journal-title":"J. Biol. Chem."},{"key":"7360_CR48","doi-asserted-by":"publisher","first-page":"1819","DOI":"10.1097\/BRS.0b013e31824ee8f7","volume":"37","author":"LA Nasto","year":"2012","unstructured":"Nasto, L. A. et al. ISSLS prize winner: inhibition of NF-\u03baB activity ameliorates age-associated disc degeneration in a mouse model of accelerated aging. Spine (Phila. Pa 1976) 37, 1819\u20131825 (2012).","journal-title":"Spine (Phila. Pa 1976)"},{"key":"7360_CR49","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1038\/nrrheum.2013.160","volume":"10","author":"MV Risbud","year":"2014","unstructured":"Risbud, M. V. et al. Role of cytokines in intervertebral disc degeneration: pain and disc-content. Nat. Rev. Rheumatol. 10, 44\u201356 (2014).","journal-title":"Nat. Rev. Rheumatol."},{"key":"7360_CR50","doi-asserted-by":"publisher","first-page":"16761","DOI":"10.1074\/jbc.M112.446633","volume":"288","author":"H Wang","year":"2013","unstructured":"Wang, H. et al. Inflammatory cytokines induce NOTCH signaling in nucleus pulposus cells implications in intervertebral disc degeneration. J. Biol. Chem. 288, 16761\u201316774 (2013).","journal-title":"J. Biol. Chem."},{"key":"7360_CR51","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1007\/s00109-015-1371-2","volume":"94","author":"ML Ji","year":"2016","unstructured":"Ji, M. L. et al. Downregulation of microRNA-193a-3p is involved in invertebral disc degeneration by targeting MMP14. J. Mol. Med. (Berl.) 94, 457\u2013468 (2016).","journal-title":"J. Mol. Med. (Berl.)"},{"key":"7360_CR52","doi-asserted-by":"publisher","first-page":"2676","DOI":"10.1016\/j.ymthe.2017.08.009","volume":"25","author":"J Lu","year":"2017","unstructured":"Lu, J. et al. MicroRNA-218-5p as a potential target for the treatment of human osteoarthritis. Mol. Ther. 25, 2676\u20132688 (2017).","journal-title":"Mol. Ther."},{"key":"7360_CR53","doi-asserted-by":"publisher","first-page":"1873","DOI":"10.1097\/00007632-200109010-00011","volume":"26","author":"CW Pfirrmann","year":"2001","unstructured":"Pfirrmann, C. W. et al. Magnetic resonance classification of lumbar intervertebral disc degeneration. Spine (Phila. Pa 1976) 26, 1873\u20131878 (2001).","journal-title":"Spine (Phila. Pa 1976)"},{"key":"7360_CR54","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1097\/01.brs.0000253961.40910.c1","volume":"32","author":"GD O\u2019Connell","year":"2007","unstructured":"O\u2019Connell, G. D. et al. Comparison of animals used in disc research to human lumbar disc geometry. Spine (Phila. Pa 1976) 32, 328\u2013333 (2007).","journal-title":"Spine (Phila. Pa 1976)"},{"key":"7360_CR55","doi-asserted-by":"publisher","first-page":"E900","DOI":"10.1097\/BRS.0b013e31824d911c","volume":"37","author":"BL Showalter","year":"2012","unstructured":"Showalter, B. L. et al. Comparison of animal discs used in disc research to human lumbar disc: torsion mechanics and collagen content. Spine (Phila. Pa 1976) 37, E900\u2013E907 (2012).","journal-title":"Spine (Phila. Pa 1976)"},{"key":"7360_CR56","doi-asserted-by":"publisher","first-page":"E166","DOI":"10.1097\/BRS.0b013e318166e001","volume":"33","author":"JC Beckstein","year":"2008","unstructured":"Beckstein, J. C. et al. Comparison of animal discs used in disc research to human lumbar disc: axial compression mechanics and glycosaminoglycan content. Spine (Phila. Pa 1976) 33, E166\u2013E173 (2008).","journal-title":"Spine (Phila. Pa 1976)"},{"key":"7360_CR57","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1002\/path.2519","volume":"218","author":"F Yang","year":"2009","unstructured":"Yang, F. et al. Injury-induced sequential transformation of notochordal nucleus pulposus to chondrogenic and fibrocartilaginous phenotype in the mouse. J. Pathol. 218, 113\u2013121 (2009).","journal-title":"J. Pathol."},{"key":"7360_CR58","doi-asserted-by":"publisher","first-page":"1925","DOI":"10.1097\/BRS.0b013e31817c64a9","volume":"33","author":"B Han","year":"2008","unstructured":"Han, B. et al. A simple disc degeneration model induced by percutaneous needle puncture in the rat tail. Spine (Phila. Pa 1976) 33, 1925\u20131934 (2008).","journal-title":"Spine (Phila. Pa 1976)"},{"key":"7360_CR59","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1097\/01.brs.0000251013.07656.45","volume":"32","author":"MA Rousseau","year":"2007","unstructured":"Rousseau, M. A. et al. Stab incision for inducing intervertebral disc degeneration in the rat. Spine (Phila. Pa 1976) 32, 17\u201324 (2007).","journal-title":"Spine (Phila. Pa 1976)"},{"key":"7360_CR60","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1097\/01.brs.0000148152.04401.20","volume":"30","author":"K Masuda","year":"2005","unstructured":"Masuda, K. et al. A novel rabbit model of mild, reproducible disc degeneration by an anulus needle puncture: correlation between the degree of disc injury and radiological and histological appearances of disc degeneration. Spine (Phila. Pa 1976) 30, 5\u201314 (2005).","journal-title":"Spine (Phila. Pa 1976)"},{"key":"7360_CR61","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1002\/art.1780240103","volume":"24","author":"SJ Lipson","year":"1981","unstructured":"Lipson, S. J. et al. Experimental intervertebral disc degeneration: morphologic and proteoglycan changes over time. Arthritis Rheum. 24, 12\u201321 (1981).","journal-title":"Arthritis Rheum."},{"key":"7360_CR62","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1002\/jor.23637","volume":"36","author":"V Tam","year":"2018","unstructured":"Tam, V. et al. Histological and reference system for the analysis of mouse intervertebral disc. J. Orthop. Res. 36, 233\u2013243 (2018).","journal-title":"J. Orthop. Res."},{"key":"7360_CR63","doi-asserted-by":"publisher","first-page":"2631","DOI":"10.1097\/00007632-200212010-00002","volume":"27","author":"N Boos","year":"2002","unstructured":"Boos, N. et al. Classification of age-related changes in lumbar intervertebral discs: 2002 Volvo Award in basic science. Spine (Phila. Pa 1976) 27, 2631\u20132644 (2002).","journal-title":"Spine (Phila. Pa 1976)"},{"key":"7360_CR64","doi-asserted-by":"publisher","first-page":"1018","DOI":"10.1097\/00007632-200205150-00004","volume":"27","author":"HA Horner","year":"2002","unstructured":"Horner, H. A. et al. Cells from different regions of the intervertebral disc: effect of culture system on matrix expression and cell phenotype. Spine (Phila. Pa 1976) 27, 1018\u20131028 (2002).","journal-title":"Spine (Phila. Pa 1976)"},{"key":"7360_CR65","doi-asserted-by":"publisher","first-page":"2355","DOI":"10.1016\/j.ajpath.2014.05.004","volume":"184","author":"XV Qadir","year":"2014","unstructured":"Qadir, X. V. et al. miR-185 inhibits hepatocellular carcinoma growth by targeting the DNMT1\/PTEN\/Akt pathway. Am. J. Pathol. 184, 2355\u20132364 (2014).","journal-title":"Am. J. Pathol."}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41467-018-07360-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-018-07360-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-018-07360-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,12]],"date-time":"2024-07-12T13:41:47Z","timestamp":1720791707000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41467-018-07360-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11,28]]},"references-count":65,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2018,12]]}},"alternative-id":["7360"],"URL":"https:\/\/doi.org\/10.1038\/s41467-018-07360-1","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,11,28]]},"assertion":[{"value":"23 January 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 October 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 November 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"5051"}}