{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:55:05Z","timestamp":1787320505025,"version":"build-2736575974"},"reference-count":44,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,3,11]],"date-time":"2018-03-11T00:00:00Z","timestamp":1520726400000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000341","name":"Arthritis Research UK","doi-asserted-by":"publisher","award":["19884"],"award-info":[{"award-number":["19884"]}],"id":[{"id":"10.13039\/501100000341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/J014478\/1"],"award-info":[{"award-number":["BB\/J014478\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JOR Spine"],"published-print":{"date-parts":[[2018,3]]},"abstract":"<jats:sec>\n                    <jats:label\/>\n                    <jats:p>Mechanical stimulation is known to influence intervertebral disc (IVD) cell behavior and function, but the effect on disc cells is routinely considered in isolation from other microenvironmental factors. Acidic pH has been shown to be a prominent and detrimental microenvironmental factor present in degenerate IVDs, but its influence on the human disc cell mechanoresponse has never been studied. We investigated the response of agarose\u2010encapsulated human nucleus pulposus (NP) cells to 0.004\u2009MPa, 1.0 Hz and 1 hour of compression (Flexcell FX4000 Compression System) under pH conditions representative of nondegenerate (pH 7.1) and degenerate (pH 6.5) IVDs. Cell viability, extracellular matrix production, and expression of anabolic\/anti\u2010catabolic and catabolic genes were assessed. We report that preculture of NP cells in agarose gels was required in order for cells to be mechanoresponsive, and this correlated with increased type VI collagen, \u03b15\u03b21 integrin, and fibronectin expression. Furthermore, the matrix homeostatic response observed at pH 7.1 (representative of nondegenerate IVDs; increased aggrecan [AGC], tissue inhibitor of metalloproteinases\u20101 [TIMP1], matrix metalloproteinase\u20103 [MMP3], a disintegrin and metalloproteinase with thrombospondin motif\u20105 [ADAMTS5] gene expression) was RGD\u2010integrin dependent, whereas only MMP3 remained mechanoresponsive at pH 6.5, and this was independent of RGD\u2010integrins. Our findings suggest differential mechanotransduction pathways operating for specific genes, with RGD\u2010integrin dependent AGC expression, but not RGD\u2010independent MMP3 expression, inhibited at pH representative of degenerate IVDs (pH 6.5), which could contribute to the catabolic phenotype observed during IVD degeneration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical significance<\/jats:title>\n                    <jats:p>Characterizing the influence of the mechanical and chemical intervertebral disc microenvironment on disc cells, particularly in disc degeneration, could help develop future therapeutic strategies for the treatment of discogenic back pain.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jsp2.1004","type":"journal-article","created":{"date-parts":[[2018,3,11]],"date-time":"2018-03-11T22:10:39Z","timestamp":1520806239000},"source":"Crossref","is-referenced-by-count":23,"title":["Degenerate intervertebral disc\u2010like pH induces a catabolic mechanoresponse in human nucleus pulposus cells"],"prefix":"10.1002","volume":"1","author":[{"given":"Nathan W.","family":"Hodson","sequence":"first","affiliation":[{"name":"Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonal","family":"Patel","sequence":"additional","affiliation":[{"name":"Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7637-4135","authenticated-orcid":false,"given":"Stephen M.","family":"Richardson","sequence":"additional","affiliation":[{"name":"Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4876-5208","authenticated-orcid":false,"given":"Judith A.","family":"Hoyland","sequence":"additional","affiliation":[{"name":"Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health University of Manchester  Manchester UK"},{"name":"NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester NHS Foundation Trust Manchester Academic Health Science Centre  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2571-765X","authenticated-orcid":false,"given":"Hamish T. J.","family":"Gilbert","sequence":"additional","affiliation":[{"name":"Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health University of Manchester  Manchester UK"},{"name":"Wellcome Trust Centre for Cell\u2010Matrix Research, Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,3,11]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ar.1092200402"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007632-198101000-00020"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007632-199904150-00005"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00586-013-2855-9"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.1100050406"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.22203\/eCM.v032a03"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1346.011"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.27643"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/BRS.0b013e318158cb61"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.20867"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.BRS.0000061985.15849.A9"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.orthres.2005.01.020"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1529-9430(01)00056-0"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00586-006-0112-1"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007632-200006150-00005"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.20253"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0268-0033(01)00080-8"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar3229"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0072994"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1042\/bst0300858"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.brs.0000154619.38122.47"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00586-003-0616-x"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar629"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02146615"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.3109\/17453676908989482"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep37360"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.21481"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1136\/mp.55.2.91"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2009.63"},{"key":"e_1_2_6_31_1","unstructured":"EsserP.pH and pressure in closed tissue culture vessels;2010.https:\/\/www.thermoscientific.com\/content\/dam\/tfs\/LPG\/LCD\/LCDDocuments\/Application\u2009%26\u2009Technical\u2009Notes\/Cell\u2009Culture\u2009Vessels\u2009and\u2009Microplates\/Cell\u2009Culture\u2009Systems\/pH\u2009and\u2009pressure\u2009issues\u2009in\u2009closed\u2009cell\u2009culture\u2009vessels.pdf. Accessed February 23 2018."},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11517-010-0681-3"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.21232"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1097\/BRS.0b013e31815b75fb"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.38049"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2003.09.099"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2007.03.008"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(82)90027-7"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.spinee.2011.07.004"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.24248"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2009.05.039"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1039\/C5TB02060C"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)33379-9"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0015746"}],"container-title":["JOR SPINE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjsp2.1004","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jsp2.1004","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jsp2.1004","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jsp2.1004","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,9]],"date-time":"2023-09-09T14:47:40Z","timestamp":1694270860000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jsp2.1004"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,3]]},"references-count":44,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2018,3]]}},"alternative-id":["10.1002\/jsp2.1004"],"URL":"https:\/\/doi.org\/10.1002\/jsp2.1004","archive":["Portico"],"relation":{},"ISSN":["2572-1143","2572-1143"],"issn-type":[{"value":"2572-1143","type":"print"},{"value":"2572-1143","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,3]]},"article-number":"e1004"}}