{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T19:19:10Z","timestamp":1789067950166,"version":"build-2803163510"},"reference-count":54,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,10,4]],"date-time":"2017-10-04T00:00:00Z","timestamp":1507075200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000341","name":"Arthritis Research UK","doi-asserted-by":"publisher","award":["19205"],"award-info":[{"award-number":["19205"]}],"id":[{"id":"10.13039\/501100000341","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":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:sec><jats:label\/><jats:p>Arterial medial calcification (AMC) is thought to share some outward similarities to skeletal mineralization and has been associated with the transdifferentiation of vascular smooth muscle cells (VSMCs) to an osteoblast\u2010like phenotype. ATP and UTP have previously been shown to inhibit bone mineralization. This investigation compared the effects of extracellular nucleotides on calcification in VSMCs with those seen in osteoblasts. ATP, UTP and the ubiquitous mineralization inhibitor, pyrophosphate (PP<jats:sub>i<\/jats:sub>), dose dependently inhibited VSMC calcification by \u226485%. Culture of VSMCs in calcifying conditions was associated with an increase in apoptosis; treatment with ATP, UTP, and PP<jats:sub>i<\/jats:sub> reduced apoptosis to levels seen in non\u2010calcifying cells. Extracellular nucleotides had no effect on osteoblast viability. Basal alkaline phosphatase (TNAP) activity was over 100\u2010fold higher in osteoblasts than VSMCs. ATP and UTP reduced osteoblast TNAP activity (\u226450%) but stimulated VSMC TNAP activity (\u226488%). The effects of extracellular nucleotides on VSMC calcification, cell viability and TNAP activity were unchanged by deletion or inhibition of the P2Y<jats:sub>2<\/jats:sub> receptor. Conversely, the actions of ATP\/UTP on bone mineralization and TNAP activity were attenuated in osteoblasts lacking the P2Y<jats:sub>2<\/jats:sub> receptor. Ecto\u2010nucleotide pyrophosphatase\/phosphodiesterase 1 (NPP1) hydrolyses ATP and UTP to produce PP<jats:sub>i<\/jats:sub>. In both VSMCs and osteoblasts, deletion of NPP1 blunted the inhibitory effects of extracellular nucleotides suggesting involvement of P2 receptor independent pathways. Our results show that although the overall functional effect of extracellular nucleotides on AMC and bone mineralization is similar there are clear differences in the cellular mechanisms mediating these actions.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcp.26166","type":"journal-article","created":{"date-parts":[[2017,10,4]],"date-time":"2017-10-04T11:48:37Z","timestamp":1507117717000},"page":"3230-3243","source":"Crossref","is-referenced-by-count":43,"title":["Inhibition of arterial medial calcification and bone mineralization by extracellular nucleotides: The same functional effect mediated by different cellular mechanisms"],"prefix":"10.1002","volume":"233","author":[{"given":"Jessal J.","family":"Patel","sequence":"first","affiliation":[{"name":"Department of Comparative Biomedical Sciences Royal Veterinary College London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongxing","family":"Zhu","sequence":"additional","affiliation":[{"name":"Guangzhou Institute of Cardiovascular Disease School of Basic Medical Sciences Guangzhou Medical University China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Britt","family":"Opdebeeck","sequence":"additional","affiliation":[{"name":"Laboratory of Pathophysiology Department of Biomedical Sciences University of Antwerp Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"D'Haese","sequence":"additional","affiliation":[{"name":"Laboratory of Pathophysiology Department of Biomedical Sciences University of Antwerp Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 L.","family":"Mill\u00e1n","sequence":"additional","affiliation":[{"name":"Sanford Burnham Prebys Medical Discovery Institute La Jolla California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucie E.","family":"Bourne","sequence":"additional","affiliation":[{"name":"Department of Comparative Biomedical Sciences Royal Veterinary College London UK"}],"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"}]},{"given":"Timothy R.","family":"Arnett","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicky E.","family":"MacRae","sequence":"additional","affiliation":[{"name":"The Roslin Institute and Royal (Dick) School of Veterinary Studies University of Edinburgh Edinburgh 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":[[2017,10,4]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0163-7258(94)00048-4"},{"issue":"2","key":"e_1_2_7_3_1","first-page":"237","article-title":"Calcification of rachitic rat cartilage in vitro by extracellular matrix vesicles","volume":"79","author":"Anderson H. C.","year":"1975","journal-title":"The American Journal of Pathology"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)62481-9"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00043.2006"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11302-013-9381-4"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-3623(85)90001-1"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.113.008029"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.3109\/10408369109106862"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2012.02.003"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0700961"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/eci.12055"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/195911a0"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.2741\/3912"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2014.09.016"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.10236"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.37.26454"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2003.18.6.994"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcm.2012.07.009"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0703744"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbf.3005"},{"issue":"2","key":"e_1_2_7_22_1","doi-asserted-by":"crossref","first-page":"32177","DOI":"10.1371\/journal.pone.0032177","article-title":"Altered bone development and an increase in FGF\u201023 expression in Enpp1(\u2010\/\u2010) mice","volume":"7","author":"Mackenzie N. C.","year":"2012","journal-title":"PLoS ONE"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.070714"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.14-257923"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.25303"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.23014"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autneu.2015.04.013"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2016.03.003"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-17-0042"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2014.1926"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2012.06.013"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0069057"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.25041"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2006.02.063"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-61779-415-5_3"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2007-0066"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M605620200"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00619.2008"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00419.2009"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.87.11.1055"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2016.12.014"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63996-X"},{"key":"e_1_2_7_43_1","first-page":"267","volume-title":"Ecto\u2010ATPases and related ectonucleotides","author":"Sali A.","year":"1999"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2011.326"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2420"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1525-139X.2007.00255.x"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00774-013-0493-2"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/bonekey.2014.80"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1253\/circj.CJ-13-0016"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01020.2010"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-200212000-00005"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0108417"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00404070"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2012.00095"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0019595"}],"container-title":["Journal of Cellular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcp.26166","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcp.26166","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,17]],"date-time":"2023-09-17T11:40:15Z","timestamp":1694950815000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcp.26166"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,10,4]]},"references-count":54,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2018,4]]}},"alternative-id":["10.1002\/jcp.26166"],"URL":"https:\/\/doi.org\/10.1002\/jcp.26166","archive":["Portico"],"relation":{},"ISSN":["0021-9541","1097-4652"],"issn-type":[{"value":"0021-9541","type":"print"},{"value":"1097-4652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,10,4]]}}}