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Ruiz-Gaspa, SCorresponding AuthorGuanabens, NAuthorCombalia, AAuthorPeris, PAuthorMonegal, AAuthorPares, AAuthor
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Ursodeoxycholic acid decreases bilirubin-induced osteoblast apoptosis

Publicated to:European Journal Of Clinical Investigation. 44 (12): 1206-1214 - 2014-12-01 44(12), DOI: 10.1111/eci.12355

Authors: Ruiz-Gaspa, Silvia; Dubreuil, Marta; Guanabens, Nuria; Combalia, Andres; Peris, Pilar; Monegal, Ana; Pares, Albert

Affiliations

Univ Barcelona, Ctr Invest Biomed Red Enfermedades Hepat & Digest, Barcelona, Spain - Author
Univ Barcelona, Dept Rheumatol, Metab Bone Dis Unit, Barcelona, Spain - Author
Univ Barcelona, IDIBAPS, Hosp Clin, Liver Unit,Digest Dis Inst, Barcelona, Spain - Author
Universitat de Barcelona - Author

Abstract

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.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 BAX) and anti-apoptotic (BCL2 and BCL2-like 1 protein, BCL2L) genes.Both LCA (10 ?M) and bilirubin (50 ?M) induced apoptosis as indicated by DNA fragmentation (4·7- and 3·7-fold, respectively, P < 0·001), caspase-3 activity and flow cytometry in Saos-2 and hOB. UDCA (10 ?M) reduced the apoptotic effects of camptothecin (0·5 ?M) by 61%, (P < 0·001) and counteracted the apoptotic effects of LCA and bilirubin determined by DNA fragmentation (56% and 60%, respectively, P < 0·001), cytometry and caspase-3 activity in Saos-2, with lower effects in hOB. UDCA (10 ?M) downregulated BAX (75%), upregulated BCL2L (10-fold, P < 0·01) genes, and neutralised BAX upregulation (P < 0·01) and BCL2L downregulation (P < 0·01) induced by LCA and bilirubin.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.© 2014 Stichting European Society for Clinical Investigation Journal Foundation.

Keywords
bile acidsbile-acidsbone turnoverbone-diseasecell-deathcholestasislithocholic acidmechanismmodulationosteoporosisprimary biliary cirrhosisproliferationtauroursodeoxycholic acidAntineoplastic agents, phytogenicAntioxidantsApoptosisBcl-2-associated x proteinBile acidsBilirubinBone turnoverCamptothecinCell line, tumorCholagogues and cholereticsCholestasisDetergentsHumansLithocholic acidOsteoblastsOsteoporosisPrimary biliary cirrhosisPrimary biliary-cirrhosisUp-regulationUrsodeoxycholic acid

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal European Journal Of Clinical Investigation due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2014, it was in position 30/154, thus managing to position itself as a Q1 (Primer Cuartil), in the category Medicine, General & Internal.

From a relative perspective, and based on the normalized impact indicator calculated from the Field Citation Ratio (FCR) of the Dimensions source, it yields a value of: 4.88, which indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: Dimensions Apr 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-04-30, the following number of citations:

  • WoS: 19
  • Scopus: 25
  • Europe PMC: 12
  • OpenCitations: 28
Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-04-30:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 28.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 28 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 3.
Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: HOBOKEN.

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (Ruiz Gaspà, Sílvia) and Last Author (Parés Darnaculleta, Albert).

the author responsible for correspondence tasks has been Ruiz Gaspà, Sílvia.