{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T05:05:00Z","timestamp":1791695100977,"version":"4.3.4"},"reference-count":63,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,10,17]],"date-time":"2021-10-17T00:00:00Z","timestamp":1634428800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000833","name":"Rosetrees Trust","doi-asserted-by":"publisher","award":["M744"],"award-info":[{"award-number":["M744"]}],"id":[{"id":"10.13039\/501100000833","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["PG\/15\/13\/31296"],"award-info":[{"award-number":["PG\/15\/13\/31296"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Arterial medial calcification (AMC) is the deposition of calcium phosphate in the arteries. AMC is widely thought to share similarities with physiological bone formation; however, emerging evidence suggests several key differences between these processes.<jats:italic>N<\/jats:italic>\u2010acetylcysteine (NAC) displays antioxidant properties and can generate hydrogen sulphide (H<jats:sub>2<\/jats:sub>S) and glutathione (GSH) from its deacetylation to<jats:sc>l<\/jats:sc>\u2010cysteine. This study found that NAC exerts divergent effects in vitro, increasing osteoblast differentiation and bone formation by up to 5.5\u2010fold but reducing vascular smooth muscle cell (VSMC) calcification and cell death by up to 80%. In vivo, NAC reduced AMC in a site\u2010specific manner by 25% but had no effect on the bone. The actions of<jats:sc>l<\/jats:sc>\u2010cysteine and H<jats:sub>2<\/jats:sub>S mimicked those of NAC; however, the effects of H<jats:sub>2<\/jats:sub>S were much less efficacious than NAC and<jats:sc>l<\/jats:sc>\u2010cysteine. Pharmacological inhibition of H<jats:sub>2<\/jats:sub>S\u2010generating enzymes did not alter the actions of NAC or<jats:sc>l<\/jats:sc>\u2010cysteine;\u00a0endogenous production of H<jats:sub>2<\/jats:sub>S was also unaffected. In contrast, NAC and<jats:sc>l<\/jats:sc>\u2010cysteine increased GSH levels in calcifying VSMCs and osteoblasts by up to 3\u2010fold. This suggests that the beneficial actions of NAC are likely to be mediated via the breakdown of<jats:sc>l<\/jats:sc>\u2010cysteine and the subsequent GSH generation. Together, these data show that while the molecular mechanisms driving the actions of NAC appear similar, the downstream effects on cell function differ significantly between osteoblasts and calcifying VSMCs. The ability of NAC to exert these differential actions further supports the notion that there are differences between the development of pathological AMC and physiological bone formation. NAC could represent a therapeutic option for treating AMC without exerting negative effects on bone.<\/jats:p>","DOI":"10.1002\/jcp.30605","type":"journal-article","created":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T06:08:21Z","timestamp":1634796501000},"page":"1070-1086","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["<i>N<\/i>\u2010acetylcysteine (NAC) differentially affects arterial medial calcification and bone formation: The role of<scp>l<\/scp>\u2010cysteine and hydrogen sulphide"],"prefix":"10.1002","volume":"237","author":[{"given":"Lucie E.","family":"Bourne","sequence":"first","affiliation":[{"name":"Department of Comparative Biomedical Sciences Royal Veterinary College London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessal J.","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Comparative Biomedical Sciences Royal Veterinary College London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bethan K.","family":"Davies","sequence":"additional","affiliation":[{"name":"Department of Comparative Biomedical Sciences Royal Veterinary College London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"Neven","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Laboratory of Pathophysiology University of Antwerp Antwerp Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Verhulst","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Laboratory of Pathophysiology University of Antwerp Antwerp Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick C.","family":"D'Haese","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Laboratory of Pathophysiology University of Antwerp Antwerp Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline P. D.","family":"Wheeler\u2010Jones","sequence":"additional","affiliation":[{"name":"Department of Comparative Biomedical Sciences Royal Veterinary College London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7847-050X","authenticated-orcid":false,"given":"Isabel R.","family":"Orriss","sequence":"additional","affiliation":[{"name":"Department of Comparative Biomedical Sciences Royal Veterinary College London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,10,17]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-15-965"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-007-9089-y"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.119.312509"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-33149-9"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-20-0428"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M800021200"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14772"},{"key":"e_1_2_8_9_1","first-page":"4337","article-title":"N\u2010acetylcysteine prevents orchiectomy\u2010induced osteoporosis by inhibiting oxidative stress and osteocyte senescence","volume":"11","author":"Chen L.","year":"2019","journal-title":"American Journal of Translational Reearch"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2016.09.071"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vph.2016.11.006"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2007.04.003"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1517\/14728220802517901"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vph.2017.05.004"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvy010"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2008.03.024"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1177\/026119290102900409"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2757"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2014.09.016"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-016-2778-y"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2005.00332.x"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.87.7.e10"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.21508"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.22846"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2015.04.017"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.3059"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0143686"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1302193110"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2014.03.005"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ki.5000297"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(01)00610-4"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfn757"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.070714"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2585"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2016.03.004"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-17-0042"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2007-0066"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/4178021"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2019.04.020"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11302-019-09672-3"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.30036"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-3628-1_6"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.26166"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-8997-3_2"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.378"},{"key":"e_1_2_8_47_1","first-page":"1","article-title":"Cystathionine beta synthase deficiency affects mouse endochondral ossification","volume":"282","author":"Robert K.","year":"2005","journal-title":"Anatatomical Record Part A: Discoveries in Molecular, Cellular and Evolutionary Biology"},{"key":"e_1_2_8_48_1","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1111\/febs.12075","article-title":"Role of GSH\/GSSG redox couple in osteogenic activity and osteoclastogenic markers of human osteoblast\u2010like SaOS\u20102 cells","volume":"280","author":"Romagnoli C.","year":"2013","journal-title":"FEBS Journal"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2013.09.006"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.110.234914"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2012.11.006"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.4.13.2210157"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2019.7723"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-20241-3"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/bonekey.2014.80"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2013.04.064"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00404070"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1007\/s000180300001"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2011.212"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.transproceed.2016.10.023"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12986-018-0296-5"},{"key":"e_1_2_8_62_1","first-page":"731","article-title":"Suppression effect of N\u2010acetylcysteine on bone loss in ovariectomized mice","volume":"12","author":"Zhou X.","year":"2020","journal-title":"American Journal of Translational Research"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0019595"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1111\/apha.12515"}],"container-title":["Journal of Cellular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcp.30605","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcp.30605","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcp.30605","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,11]],"date-time":"2023-11-11T13:31:55Z","timestamp":1699709515000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcp.30605"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,17]]},"references-count":63,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,1]]}},"alternative-id":["10.1002\/jcp.30605"],"URL":"https:\/\/doi.org\/10.1002\/jcp.30605","archive":["Portico"],"relation":{},"ISSN":["0021-9541","1097-4652"],"issn-type":[{"value":"0021-9541","type":"print"},{"value":"1097-4652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,17]]},"assertion":[{"value":"2021-05-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-09-08","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-10-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}