{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T17:35:33Z","timestamp":1760204133751},"reference-count":41,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2006,1,26]],"date-time":"2006-01-26T00:00:00Z","timestamp":1138233600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2006,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Atherosclerosis is epidemiologically associated with postmenopausal osteoporosis (OP) presumably by common etiologic factors, reflecting a state of co\u2010morbidity in aging. Osteoblasts make a significant facet of this co\u2010morbidity state. Since oxidized low\u2010density lipoprotein (oxLDL) is a major factor in generation of vascular wall pathology, we examined the ability of native LDL (nLDL) and oxLDL to induce Saos2 osteoblasts growth arrest. OxLDL induced Saos2 cell death with morphological features of apoptosis that was inhibited mainly by caspase\u20109 and partially by caspase\u20103 but not by caspase\u20108 inhibitors. nLDL, like oxLDL, has induced cell death, where 60% (<jats:italic>P<\/jats:italic>\u2009=\u20090.00033) and 30% (<jats:italic>P<\/jats:italic>\u2009=\u20090.075, ns) of the cell death, respectively, could be inhibited by scyphostatin (a neutral sphingomyelinase [nSMase] inhibitor). Upon similar condition, nLDL inhibited the phosphorylation of Akt and two of its downstream targets, fork head receptor (FKHR) and glycogen synthase kinase\u20103 (GSK3). This is a pathway that stimulates cell survival and proliferation. nLDL has also induced an increase in the proapoptotic Bcl\u2010Xs and it has diminished the potential antiapoptotic Src kinase activity. At the 4 h time\u2010point, upon a substantial decrease in nLDL\u2010induced Akt phosphorylation, scyphostatin has inhibited the reduction in FKHR and GSK3 phosphorylation but inexplicably not that of Akt. Scyphostatin has also corrected the reduction in Src kinase activity. Taken together, the results indicate that nLDL has induced apoptosis in Saos2 osteoblasts by inactivation of the pathway downstream to Akt using nSMase, and by involvement of Src kinase. Inferring that caspase\u20109 was the main executioner (rather than caspase\u20108 and\u20103) in Saos2 cell death, indicates that the nSMase\u2010induced release of ceramide, directly activated the intrinsic mitochondrial apoptotic pathway. With regard to the Akt inactivation by nLDL, Saos2 osteoblasts responded in an opposite fashion to the response reported by others, in macrophages. J. Cell. Biochem. 98: 661\u2013671, 2006. \u00a9 2006 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcb.20807","type":"journal-article","created":{"date-parts":[[2006,1,26]],"date-time":"2006-01-26T20:46:44Z","timestamp":1138308404000},"page":"661-671","source":"Crossref","is-referenced-by-count":8,"title":["LDL induces Saos2 osteoblasts death via Akt pathways responsive to a neutral sphingomyelinase inhibitor"],"prefix":"10.1002","volume":"98","author":[{"given":"Benjamin Y.","family":"Klein","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zohar","family":"Kerem","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathan","family":"Rojansky","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,1,26]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000043453.21629.3B"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002239900419"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116032"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1258\/0004563021902134"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00170.2004"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000113782.07824.BE"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)39807-2"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2005.02.029"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1124\/mi.3.8.436"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-8981(99)00103-5"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.2174\/1381612013397762"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1010987220034"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(03)00468-6"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.20.8.1926"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/qjmed\/hci077"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0925-4773(96)88032-4"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)30282-0"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M209179200"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(03)00929-2"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1601-0825.2002.01797.x"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1006\/mcbr.2000.0197"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(01)00258-1"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2001.tb03941.x"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4644(19980601)69:3<316::AID-JCB9>3.0.CO;2-U"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.10603"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000119804.92239.97"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.48.2.352-360.1983"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401399"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.151.2.311"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1385\/ENDO:23:1:01"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1368-8375(02)00019-2"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.99-0986com"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.52.531"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2003-0746"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.2174\/1568008043340044"},{"key":"e_1_2_5_37_1","first-page":"769","article-title":"Sialic acids linked to glycoconjugates of Fas regulate the caspase\u20109\u2010dependent and mitochondria\u2010mediated pathway of Fas\u2010induced apoptosis in Jurkat T cell lymphoma","volume":"23","author":"Suzuki O","year":"2003","journal-title":"Int J Oncol"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1526-0968.2000.004002135.x"},{"key":"e_1_2_5_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-002-2070-x"},{"key":"e_1_2_5_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9150(00)00573-6"},{"key":"e_1_2_5_41_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000130527.92537.06"},{"key":"e_1_2_5_42_1","first-page":"1347","article-title":"Overexpression of the Csk homologous kinase facilitates phosphorylation of Akt\/PKB in MCF\u20107 cells","volume":"21","author":"Zagozdzon R","year":"2002","journal-title":"Int J Oncol"}],"container-title":["Journal of Cellular Biochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcb.20807","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcb.20807","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T22:53:35Z","timestamp":1697669615000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcb.20807"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,1,26]]},"references-count":41,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2006,6]]}},"alternative-id":["10.1002\/jcb.20807"],"URL":"https:\/\/doi.org\/10.1002\/jcb.20807","archive":["Portico"],"relation":{},"ISSN":["0730-2312","1097-4644"],"issn-type":[{"value":"0730-2312","type":"print"},{"value":"1097-4644","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,1,26]]}}}