Ursodeoxycholic acid decreases bilirubin‐induced osteoblast apoptosis. (9th November 2014)

• Record Type: Journal Article
• Authors: Ruiz‐Gaspà, Silvia; Dubreuil, Marta; Guañabens, Nuria; Combalia, Andrés; Peris, Pilar; Monegal, Ana; Parés, Albert
• Is Part Of: European journal of clinical investigation. Volume 44:Number 12(2014:Dec.)
• Page Start: 1206
• Page End: 1214
• Publication Date: 2014-11-09
• Subjects: Pathology -- Periodicals; Medical research -- Periodicals; 616.075
• DOI: 10.1111/eci.12355
• Languages: English
• ISSNs: 0014-2972

Abstract

<abstract abstract-type="main" id="eci12355-abs-0001"> <title>Abstract</title> <sec id="eci12355-sec-0001" sec-type="section"> <title>Background</title> <p>Low bone turnover osteoporosis is common in cholestatic diseases. Ursodeoxycholic acid (UDCA) counteracts the damaging effects of bilirubin or lithocholic acid (LCA) on osteoblast viability, proliferation and mineralisation. UDCA is anti‐apoptotic in various cell lines, but this effect in bone cells is unknown. Therefore, the consequences of bilirubin and LCA on apoptosis, and whether UDCA has anti‐apoptotic effects have been assessed on osteoblasts.</p> </sec> <sec id="eci12355-sec-0002" sec-type="section"> <title>Materials and Methods</title> <p>Human osteoblasts (hOB) and osteosarcoma cell line (Saos‐2) were treated with camptothecin as a pro‐apoptotic agent, and UDCA, LCA and bilirubin. Apoptosis was determined by DNA fragmentation, flow cytometry, caspase‐3 activity and expression of pro‐apoptotic (Bcl‐2‐associated X protein <italic>BAX</italic>) and anti‐apoptotic (<italic>BCL2</italic> and BCL2‐like 1 protein, <italic>BCL2L</italic>) genes.</p> </sec> <sec id="eci12355-sec-0003" sec-type="section"> <title>Results</title> <p>Both LCA (10 μM) and bilirubin (50 μM) induced apoptosis as indicated by DNA fragmentation (4·7‐ and 3·7‐fold, respectively, <italic>P</italic> < 0·001), caspase‐3 activity and flow cytometry in Saos‐2 and hOB. UDCA (10 μM) reduced the apoptotic effects of camptothecin (0·5 μM) by 61%, (<italic>P</italic> < 0·001) and counteracted the apoptotic effects of LCA and bilirubin determined by DNA fragmentation (56% and 60%, respectively, <italic>P</italic> < 0·001), cytometry and caspase‐3 activity in Saos‐2, with lower effects in hOB. UDCA (10 μM) downregulated <italic>BAX</italic> (75%), upregulated <italic>BCL2L</italic> (10‐fold, <italic>P</italic> < 0·01) genes, and neutralised <italic>BAX</italic> upregulation (<italic>P</italic> < 0·01) and <italic>BCL2L</italic> downregulation (<italic>P</italic> < 0·01) induced by LCA and bilirubin.</p> </sec> <sec id="eci12355-sec-0004" sec-type="section"> <title>Conclusions</title> <p>Bilirubin and LCA induce apoptosis in osteoblastic cells. UDCA counteracts the apoptotic consequences of these two substances, and therefore, it may have further beneficial effects on the decreased bone formation in the cholestasis.</p> </sec> </abstract>