{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T07:18:01Z","timestamp":1788333481655,"version":"build-2803163510"},"reference-count":38,"publisher":"American Chemical Society (ACS)","issue":"17","license":[{"start":{"date-parts":[[2017,8,21]],"date-time":"2017-08-21T00:00:00Z","timestamp":1503273600000},"content-version":"vor","delay-in-days":32,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_ccbyncnd_termsofuse.html"}],"funder":[{"DOI":"10.13039\/501100006315","name":"Reumafonds","doi-asserted-by":"publisher","award":["13-2-402"],"award-info":[{"award-number":["13-2-402"]}],"id":[{"id":"10.13039\/501100006315","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/na","name":"Provinz Limburg","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,9,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Articular cartilage is exposed to a gradient of oxygen levels ranging from 5% at the surface to 1% in the deepest layers. While most cartilage research is performed in supraphysiological oxygen levels (19\u201321%), culturing chondrocytes under hypoxic oxygen levels (\u22648%) promotes the chondrogenic phenotype. Exposure of cells to various oxygen levels alters their lipid metabolism, but detailed studies examining how hypoxia affects lipid metabolism in chondrocytes are lacking. To better understand the chondrocyte\u2019s behavior in response to oxygen, we cultured 3D pellets of human primary chondrocytes in normoxia (20% oxygen) and hypoxia (2.5% oxygen) and employed matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) in order to characterize the lipid profiles and their spatial distribution. In this work we show that chondrocytes cultured in hypoxia and normoxia can be differentiated by their lipid profiles. Among other species, phosphatidylglycerol species were increased in normoxic pellets, whereas phosphatidylinositol species were the most prominent lipids in hypoxic pellets. Moreover, spatial mapping revealed that phospahtidylglyycerol species were less prominent in the center of pellets where the oxygen level is lower. Additional analysis revealed a higher abundance of the mitochondrial-specific lipids, cardiolipins, in normoxic conditions. In conclusion MALDI-MSI described specific lipid profiles that could be used as sensors of oxygen level changes and may especially be relevant for retaining the chondrogenic phenotype, which has important implications for the treatment of bone and cartilage diseases.<\/jats:p>","DOI":"10.1021\/acs.analchem.7b02265","type":"journal-article","created":{"date-parts":[[2017,7,20]],"date-time":"2017-07-20T12:42:59Z","timestamp":1500554579000},"page":"9438-9444","source":"Crossref","is-referenced-by-count":17,"title":["Oxygen-Dependent Lipid Profiles of Three-Dimensional\nCultured Human Chondrocytes Revealed by MALDI-MSI"],"prefix":"10.1021","volume":"89","author":[{"given":"Brenda","family":"Bakker","sequence":"first","affiliation":[{"name":"University of Twente , , ,","place":["Enschede, The Netherlands, 7522 NB"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gert B.","family":"Eijkel","sequence":"additional","affiliation":[{"name":"Maastricht University , , ,","place":["Maastricht, The Netherlands, 6229 ER"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6533-7179","authenticated-orcid":true,"given":"Ron M. A.","family":"Heeren","sequence":"additional","affiliation":[{"name":"Maastricht University , , ,","place":["Maastricht, The Netherlands, 6229 ER"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel","family":"Karperien","sequence":"additional","affiliation":[{"name":"University of Twente , , ,","place":["Enschede, The Netherlands, 7522 NB"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janine N.","family":"Post","sequence":"additional","affiliation":[{"name":"University of Twente , , ,","place":["Enschede, The Netherlands, 7522 NB"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7407-1165","authenticated-orcid":true,"given":"Berta","family":"Cillero-Pastor","sequence":"additional","affiliation":[{"name":"Maastricht University , , ,","place":["Maastricht, The Netherlands, 6229 ER"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2017,7,20]]},"reference":[{"key":"2026090203042772000_cit1","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1098\/rstb.1975.0050","article-title":"Philosophical Transactions\nof the Royal Society of\nLondon","volume":"271","author":"Silver","year":"1975","journal-title":"Philos. Trans. R. Soc., B"},{"key":"2026090203042772000_cit2","doi-asserted-by":"publisher","first-page":"3915","DOI":"10.1002\/art.20675","volume":"50","author":"Zhou","year":"2004","journal-title":"Arthritis Rheum."},{"key":"2026090203042772000_cit3","doi-asserted-by":"publisher","first-page":"5453","DOI":"10.1073\/pnas.1514854113","volume":"113","author":"Bouaziz","year":"2016","journal-title":"Proc.\nNatl. Acad. Sci. U. S. A."},{"key":"2026090203042772000_cit4","doi-asserted-by":"publisher","first-page":"234","DOI":"10.3109\/17453674.2011.566135","volume":"82","author":"Foldager","year":"2011","journal-title":"Acta orthopaedica"},{"key":"2026090203042772000_cit5","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1053\/joca.1999.0314","volume":"8","author":"Grimshaw","year":"2000","journal-title":"Osteoarthritis and cartilage\/OARS,\nOsteoarthritis Research Society"},{"key":"2026090203042772000_cit6","doi-asserted-by":"publisher","first-page":"1585","DOI":"10.1089\/ten.tea.2009.0411","volume":"16","author":"Henderson","year":"2010","journal-title":"Tissue Eng., Part\nA"},{"key":"2026090203042772000_cit7","doi-asserted-by":"publisher","first-page":"R92","DOI":"10.1186\/ar4272","volume":"15","author":"Markway","year":"2013","journal-title":"Arthritis research\n& therapy"},{"key":"2026090203042772000_cit8","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1139\/y11-055","volume":"89","author":"Ziskoven","year":"2011","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"2026090203042772000_cit9","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1016\/j.bbadis.2016.01.003","volume":"1862","author":"Lepetsos","year":"2016","journal-title":"Biochim. Biophys. Acta, Mol. Basis Dis."},{"key":"2026090203042772000_cit10","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1002\/art.1780130606","volume":"13","author":"Lund-Olesen","year":"1970","journal-title":"Arthritis Rheum."},{"key":"2026090203042772000_cit11","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1136\/ard.50.2.124","volume":"50","author":"Stevens","year":"1991","journal-title":"Ann. Rheum. Dis."},{"key":"2026090203042772000_cit12","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1016\/j.tcb.2014.06.001","volume":"24","author":"Ackerman","year":"2014","journal-title":"Trends Cell Biol."},{"key":"2026090203042772000_cit13","doi-asserted-by":"publisher","first-page":"3981","DOI":"10.1021\/acs.analchem.5b00114","volume":"87","author":"Georgi","year":"2015","journal-title":"Anal. Chem."},{"key":"2026090203042772000_cit14","doi-asserted-by":"publisher","first-page":"5947","DOI":"10.1021\/ac504503x","volume":"87","author":"Jiang","year":"2015","journal-title":"Anal. Chem."},{"key":"2026090203042772000_cit15","doi-asserted-by":"publisher","first-page":"4642","DOI":"10.1074\/jbc.M305518200","volume":"279","author":"Wu","year":"2004","journal-title":"J. Biol. Chem."},{"key":"2026090203042772000_cit16","doi-asserted-by":"publisher","first-page":"2716","DOI":"10.1128\/MCB.01638-08","volume":"29","author":"Schmidt","year":"2009","journal-title":"Molecular and cellular\nbiology"},{"key":"2026090203042772000_cit17","doi-asserted-by":"publisher","first-page":"e62715","DOI":"10.1371\/journal.pone.0062715","volume":"8","author":"Simonaro","year":"2013","journal-title":"PLoS One"},{"key":"2026090203042772000_cit18","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1002\/pmic.201400260","volume":"15","author":"Rocha","year":"2015","journal-title":"Proteomics"},{"key":"2026090203042772000_cit19","doi-asserted-by":"publisher","first-page":"e91769","DOI":"10.1371\/journal.pone.0091769","volume":"9","author":"Kosinska","year":"2014","journal-title":"PLoS One"},{"key":"2026090203042772000_cit20","doi-asserted-by":"publisher","first-page":"8909","DOI":"10.1021\/ac301853q","volume":"84","author":"Cillero-Pastor","year":"2012","journal-title":"Anal. Chem."},{"key":"2026090203042772000_cit21","unstructured":"Wittenauer, R.; Smith, L.; Aden, K.\n          Osteoarthritis.  Priority Medicines for Europe and the World: \u201cA\nPublic Health Approach to Innovation\u201d, Update on 2004\nBackground Paper, BP 6.12; World Health Organization, 2013."},{"key":"2026090203042772000_cit22","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.joca.2009.08.010","volume":"18","author":"Blagojevic","year":"2010","journal-title":"Osteoarthritis and cartilage\/OARS,\nOsteoarthritis Research Society"},{"key":"2026090203042772000_cit23","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1016\/j.chemphyslip.2012.06.001","volume":"165","author":"Sparvero","year":"2012","journal-title":"Chem. Phys. Lipids"},{"key":"2026090203042772000_cit24","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.joca.2005.07.014","volume":"14","author":"Pritzker","year":"2006","journal-title":"Osteoarthritis\nand cartilage\/OARS, Osteoarthritis Research Society"},{"key":"2026090203042772000_cit25","doi-asserted-by":"publisher","first-page":"2397","DOI":"10.1089\/ten.2006.12.2397","volume":"12","author":"Hendriks","year":"2006","journal-title":"Tissue Eng."},{"key":"2026090203042772000_cit26","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1002\/mrd.22489","volume":"82","author":"Schindelin","year":"2015","journal-title":"Mol. Reprod. Dev."},{"key":"2026090203042772000_cit27","doi-asserted-by":"publisher","first-page":"3114","DOI":"10.1002\/rcm.4230","volume":"23","author":"Sladkova","year":"2009","journal-title":"Rapid Commun. Mass Spectrom."},{"key":"2026090203042772000_cit28","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1002\/sia.3088","volume":"41","author":"Eijkel","year":"2009","journal-title":"Surf. Interface\nAnal."},{"key":"2026090203042772000_cit29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.plipres.2014.04.001","volume":"55","author":"Ren","year":"2014","journal-title":"Prog. Lipid Res."},{"key":"2026090203042772000_cit30","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.bbalip.2016.08.010","volume":"1862","author":"Schlame","year":"2017","journal-title":"Biochim. Biophys.\nActa, Mol. Cell Biol. Lipids"},{"key":"2026090203042772000_cit31","doi-asserted-by":"publisher","first-page":"1925","DOI":"10.1089\/ars.2013.5280","volume":"20","author":"Paradies","year":"2014","journal-title":"Antioxid. Redox Signaling"},{"key":"2026090203042772000_cit32","first-page":"521","volume":"17","author":"James","year":"1990","journal-title":"J. Rheumatol."},{"key":"2026090203042772000_cit33","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1006\/taap.1996.8029","volume":"142","author":"Merrill","year":"1997","journal-title":"Toxicol.\nAppl. Pharmacol."},{"key":"2026090203042772000_cit34","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1194\/jlr.M027961","volume":"54","author":"Chughtai","year":"2013","journal-title":"J. Lipid Res."},{"key":"2026090203042772000_cit35","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/S0925-4439(98)00061-1","volume":"1408","author":"Veldhuizen","year":"1998","journal-title":"Biochim. Biophys. Acta, Mol. Basis Dis."},{"key":"2026090203042772000_cit36","doi-asserted-by":"publisher","DOI":"10.1002\/term.2126","author":"Heywood","year":"2016","journal-title":"J. Tissue Eng. Regen.\nMed."},{"key":"2026090203042772000_cit37","doi-asserted-by":"publisher","first-page":"1804","DOI":"10.1002\/mnfr.201500966","volume":"60","author":"Bradley","year":"2016","journal-title":"Mol. Nutr. Food\nRes."},{"key":"2026090203042772000_cit38","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1161\/CIRCHEARTFAILURE.113.000744","volume":"7","author":"Le","year":"2014","journal-title":"Circ.: Heart Failure"}],"container-title":["Analytical Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.analchem.7b02265","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/ancham\/article-pdf\/89\/17\/9438\/67643684\/acs.analchem.7b02265.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/ancham\/article-pdf\/89\/17\/9438\/67643684\/acs.analchem.7b02265.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T07:04:37Z","timestamp":1788332677000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/ancham\/article\/89\/17\/9438\/818160\/Oxygen-Dependent-Lipid-Profiles-of-Three"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,7,20]]},"references-count":38,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2017,7,20]]},"published-print":{"date-parts":[[2017,9,5]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.analchem.7b02265","relation":{},"ISSN":["0003-2700","1520-6882"],"issn-type":[{"value":"0003-2700","type":"print"},{"value":"1520-6882","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,7,20]]}}}