{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T22:42:54Z","timestamp":1784068974406,"version":"3.55.0"},"reference-count":51,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T00:00:00Z","timestamp":1643673600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010686","name":"H2020 European Institute of Innovation and Technology","doi-asserted-by":"publisher","award":["955735"],"award-info":[{"award-number":["955735"]}],"id":[{"id":"10.13039\/100010686","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Intervertebral disc (IVD) degeneration is a spinal disorder that triggers an inflammatory response and subsequent development of spinal pseudoarthrosis. The aim of the present study is to elucidate the role of the extracellular signal\u2010regulated kinase (ERK) pathway in inflammation\u2010induced IVD cells. Inflammatory human nucleus pulposus (NP) cells (NPCs) were induced using tumor necrosis factor\u2010\u03b1\u00a0and the ERK pathway was blocked using a selective molecule\u2010based inhibitor U0126. Gene expression of catabolic and anabolic markers, proinflammatory, and NPCs markers was investigated. The enzymatic activity of matrix metalloproteinases (MMP)2\/MMP9 was determined by gelatin zymography and nitrite production was assessed by Griess reaction. The NPC metabolic activity and viability were assessed using resazurin sodium\u2010salt and live\/dead assays, and subsequently, the specificity of U0126 on ERK1\/2 signaling was determined. The catabolic enzyme MMP3 (<jats:italic>p<\/jats:italic>\u2009=\u20090.0001) and proinflammatory cytokine interleukin 6 (<jats:italic>p<\/jats:italic>\u2009=\u20090.036)\u00a0were downregulated by U0126 in NPCs under inflammatory conditions. A significant increase of the cytokeratin 19 (<jats:italic>p<\/jats:italic>\u2009=\u20090.0031) was observed, suggesting a partial and possible recovery of the NP phenotype. U0126 does not seem to have an effect on prostaglandin production, aggrecanases, or other anabolic genes. We confirmed that U0126 selectively blocks the ERK phosphorylation and only affects the cell metabolic activity without the reduction of viable cells. Inhibition of ERK signaling downregulates important metalloproteinases and proinflammatory cytokines, and upregulates some NP markers, suggesting its potential to treat IVD degeneration.<\/jats:p>","DOI":"10.1002\/jor.25273","type":"journal-article","created":{"date-parts":[[2022,2,2]],"date-time":"2022-02-02T04:22:31Z","timestamp":1643775751000},"page":"2362-2371","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Inhibition of the extracellular signal\u2010regulated kinase pathway reduces the inflammatory component in nucleus pulposus cells"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1676-0920","authenticated-orcid":false,"given":"Adel","family":"Tekari","sequence":"first","affiliation":[{"name":"Tissue Engineering for Orthopaedics and Mechanobiology, Bone and Joint Program, Department for BioMedical Research (DBMR), Medical Faculty University of Bern Bern Switzerland"},{"name":"Laboratory of Molecular and Cellular Screening Processes, Centre of Biotechnology of Sfax University of Sfax Sfax Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1656-7418","authenticated-orcid":false,"given":"Alessandro","family":"Marazza","sequence":"additional","affiliation":[{"name":"Tissue Engineering for Orthopaedics and Mechanobiology, Bone and Joint Program, Department for BioMedical Research (DBMR), Medical Faculty University of Bern Bern Switzerland"},{"name":"Alzheimer's Center at Temple, Lewis Katz School of Medicine Temple University Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5328-667X","authenticated-orcid":false,"given":"Katherine","family":"Crump","sequence":"additional","affiliation":[{"name":"Tissue Engineering for Orthopaedics and Mechanobiology, Bone and Joint Program, Department for BioMedical Research (DBMR), Medical Faculty University of Bern Bern Switzerland"},{"name":"Department of Orthopaedic Surgery and Traumatology, Inselspital, Bern University Hospital University of Bern Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6858-8213","authenticated-orcid":false,"given":"Paola","family":"Bermudez\u2010Lekerika","sequence":"additional","affiliation":[{"name":"Tissue Engineering for Orthopaedics and Mechanobiology, Bone and Joint Program, Department for BioMedical Research (DBMR), Medical Faculty University of Bern Bern Switzerland"},{"name":"Department of Orthopaedic Surgery and Traumatology, Inselspital, Bern University Hospital University of Bern Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9005-0655","authenticated-orcid":false,"given":"Benjamin","family":"Gantenbein","sequence":"additional","affiliation":[{"name":"Tissue Engineering for Orthopaedics and Mechanobiology, Bone and Joint Program, Department for BioMedical Research (DBMR), Medical Faculty University of Bern Bern Switzerland"},{"name":"Department of Orthopaedic Surgery and Traumatology, Inselspital, Bern University Hospital University of Bern Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,2]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)60610-7"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-204428"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/BRS.0b013e31822f0a0d"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.2106\/00004623-199072030-00013"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar2275"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.7326\/M16-2367"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01358742"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000000275"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.brs.0000149194.17891.bf"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.brs.0000149186.63457.20"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1397.069"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2013.160"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar1464"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.10371"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.8.5613"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2015.11.022"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/BRS.0b013e31829a6930"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1080\/03008207.2018.1442445"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar4379"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep42938"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/jsp2.1104"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12010-010-8975-3"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tec.2016.0355"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0072489"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1177\/2049463713479096"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1097\/BRS.0000000000000428"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.2147\/JPR.S92776"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007632-198812000-00016"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.spinee.2012.02.027"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.brs.0000146101.53784.b1"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.2741\/2078"},{"key":"e_1_2_8_34_1","first-page":"4","article-title":"The aging spine: the role of inflammatory mediators in intervertebral disc degeneration","volume":"53","author":"Podichetty VK","year":"2007","journal-title":"Cell Mol Biol"},{"key":"e_1_2_8_35_1","first-page":"40","article-title":"Single intradiscal administration of the tumor necrosis factor\u2010alpha inhibitor, etanercept, for patients with discogenic low back pain","volume":"17","author":"Sainoh T","year":"2016","journal-title":"Pain Med"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.anes.0000267518.20363.0d"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1185\/030079903125004286"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar2858"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1097\/MIB.0000000000000533"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.brs.0000244616.64962.9e"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cr.7290105"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.23085"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.24332"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2011-200061"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.3109\/03008207.2015.1054030"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2017.05.013"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1369\/0022155413484765"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.06-7938com"},{"key":"e_1_2_8_49_1","first-page":"163","article-title":"Assessment of gelatinases (MMP\u20102 and MMP\u20109) by gelatin zymography","volume":"57","author":"Toth M","year":"2001","journal-title":"Methods Mol Med"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00586-014-3675-2"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2006.07.002"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2013.02.037"}],"container-title":["Journal of Orthopaedic Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jor.25273","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jor.25273","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jor.25273","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T07:57:08Z","timestamp":1692604628000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jor.25273"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2]]},"references-count":51,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2022,10]]}},"alternative-id":["10.1002\/jor.25273"],"URL":"https:\/\/doi.org\/10.1002\/jor.25273","archive":["Portico"],"relation":{},"ISSN":["0736-0266","1554-527X"],"issn-type":[{"value":"0736-0266","type":"print"},{"value":"1554-527X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2]]},"assertion":[{"value":"2021-06-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-01-16","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-02-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}