{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T12:37:11Z","timestamp":1788871031918,"version":"build-2803163510"},"reference-count":45,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2014,11,9]],"date-time":"2014-11-09T00:00:00Z","timestamp":1415491200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"crossref","award":["PI1100281"],"award-info":[{"award-number":["PI1100281"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Clin Investigation"],"published-print":{"date-parts":[[2014,12]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n \n Low bone turnover osteoporosis is common in cholestatic diseases. Ursodeoxycholic acid (\n UDCA<\/jats:styled-content>\n ) counteracts the damaging effects of bilirubin or lithocholic acid (\n LCA<\/jats:styled-content>\n ) on osteoblast viability, proliferation and mineralisation.\n UDCA<\/jats:styled-content>\n is anti\u2010apoptotic in various cell lines, but this effect in bone cells is unknown. Therefore, the consequences of bilirubin and\n LCA<\/jats:styled-content>\n on apoptosis, and whether\n UDCA<\/jats:styled-content>\n has anti\u2010apoptotic effects have been assessed on osteoblasts.\n <\/jats:p>\n <\/jats:sec>\n \n Materials and Methods<\/jats:title>\n \n Human osteoblasts (\n hOB<\/jats:styled-content>\n ) and osteosarcoma cell line (Saos\u20102) were treated with camptothecin as a pro\u2010apoptotic agent, and UDCA, LCA and bilirubin. Apoptosis was determined by DNA fragmentation, flow cytometry, caspase\u20103 activity and expression of pro\u2010apoptotic (Bcl\u20102\u2010associated X protein\n BAX<\/jats:italic>\n ) and anti\u2010apoptotic (\n BCL2<\/jats:italic>\n and BCL2\u2010like 1 protein,\n BCL2L<\/jats:italic>\n ) genes.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Both LCA (10\u00a0\u03bcM) and bilirubin (50\u00a0\u03bcM) induced apoptosis as indicated by DNA fragmentation (4\u00b77\u2010 and 3\u00b77\u2010fold, respectively,\n P<\/jats:italic>\n \u00a0<\u00a00\u00b7001), caspase\u20103 activity and flow cytometry in Saos\u20102 and\n hOB<\/jats:styled-content>\n . UDCA (10\u00a0\u03bcM) reduced the apoptotic effects of camptothecin (0\u00b75\u00a0\u03bcM) by 61%, (\n P<\/jats:italic>\n \u00a0<\u00a00\u00b7001) and counteracted the apoptotic effects of LCA and bilirubin determined by DNA fragmentation (56% and 60%, respectively,\n P<\/jats:italic>\n \u00a0<\u00a00\u00b7001), cytometry and caspase\u20103 activity in Saos\u20102, with lower effects in\n hOB<\/jats:styled-content>\n . UDCA (10\u00a0\u03bcM) downregulated\n BAX<\/jats:italic>\n (75%), upregulated\n BCL2L<\/jats:italic>\n (10\u2010fold,\n P<\/jats:italic>\n \u00a0<\u00a00\u00b701) genes, and neutralised\n BAX<\/jats:italic>\n upregulation (\n P<\/jats:italic>\n \u00a0<\u00a00\u00b701) and\n BCL2L<\/jats:italic>\n downregulation (\n P<\/jats:italic>\n \u00a0<\u00a00\u00b701) induced by LCA and bilirubin.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Bilirubin and\n LCA<\/jats:styled-content>\n induce apoptosis in osteoblastic cells.\n UDCA<\/jats:styled-content>\n counteracts the apoptotic consequences of these two substances, and therefore, it may have further beneficial effects on the decreased bone formation in the cholestasis.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/eci.12355","type":"journal-article","created":{"date-parts":[[2014,10,21]],"date-time":"2014-10-21T02:23:55Z","timestamp":1413858235000},"page":"1206-1214","source":"Crossref","is-referenced-by-count":33,"title":["Ursodeoxycholic acid decreases bilirubin\u2010induced osteoblast apoptosis"],"prefix":"10.1111","volume":"44","author":[{"given":"Silvia","family":"Ruiz\u2010Gasp\u00e0","sequence":"first","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd) Hospital Cl\u00ednic IDIBAPS University of Barcelona Barcelona Spain"},{"name":"Metabolic Bone Diseases Unit Department of Rheumatology Hospital Cl\u00ednic IDIBAPS University of Barcelona Barcelona Spain"},{"name":"Liver Unit Digestive Diseases Institute Hospital Cl\u00ednic IDIBAPS University of Barcelona Barcelona 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