Get access

Ursodeoxycholic acid increases differentiation and mineralization and neutralizes the damaging effects of bilirubin on osteoblastic cells

Authors

  • Marta Dubreuil,

    1. Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd), University of Barcelona, Barcelona, Spain
    2. Metabolic Bone Diseases Unit, Department of Rheumatology, University of Barcelona, Barcelona, Spain
    3. Liver Unit, Digestive Diseases Institute, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain
    Search for more papers by this author
    • Both authors equally contributed to this work
  • Silvia Ruiz-Gaspà,

    Corresponding author
    1. Metabolic Bone Diseases Unit, Department of Rheumatology, University of Barcelona, Barcelona, Spain
    2. Liver Unit, Digestive Diseases Institute, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain
    • Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd), University of Barcelona, Barcelona, Spain
    Search for more papers by this author
    • Both authors equally contributed to this work
  • Nuria Guañabens,

    1. Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd), University of Barcelona, Barcelona, Spain
    2. Metabolic Bone Diseases Unit, Department of Rheumatology, University of Barcelona, Barcelona, Spain
    Search for more papers by this author
  • Pilar Peris,

    1. Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd), University of Barcelona, Barcelona, Spain
    2. Metabolic Bone Diseases Unit, Department of Rheumatology, University of Barcelona, Barcelona, Spain
    Search for more papers by this author
  • Luisa Álvarez,

    1. Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd), University of Barcelona, Barcelona, Spain
    2. Metabolic Bone Diseases Unit, Department of Rheumatology, University of Barcelona, Barcelona, Spain
    Search for more papers by this author
  • Ana Monegal,

    1. Metabolic Bone Diseases Unit, Department of Rheumatology, University of Barcelona, Barcelona, Spain
    Search for more papers by this author
  • Andrés Combalia,

    1. Metabolic Bone Diseases Unit, Department of Rheumatology, University of Barcelona, Barcelona, Spain
    Search for more papers by this author
  • Albert Parés

    1. Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd), University of Barcelona, Barcelona, Spain
    2. Liver Unit, Digestive Diseases Institute, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain
    Search for more papers by this author

Correspondence

Silvia Ruiz-Gaspà, PhD,

CIBERehd,

Metabolic Bone Diseases Unit

Hospital Clinic-IDIBAPS,

Villarroel 170,

08036 Barcelona, Spain

Tel: +34 93 2275753

Fax: +34 93 2271779

e-mail: silvia.ruiz@ciberehd.org

Abstract

Background

Osteoporosis resulting from decreased bone formation is a common complication in patients with chronic cholestasis. Lithocholic acid (LCA) and bilirubin may play a role in osteoporosis given that both substances have detrimental effects on survival of human osteoblasts, the cells involved in bone formation.

Aims

As ursodeoxycholic acid (UDCA) improves cholestasis, we have assessed if this bile acid may neutralize the harmful effects of LCA, bilirubin and sera from jaundiced patients on osteoblastic cells.

Methods

The experiments were performed in primary human osteoblasts and human osteosarcoma cell line (Saos-2) at different times and concentrations of UDCA, LCA, cholic acid (CA), bilirubin and sera from jaundiced patients to assess cell viability, differentiation and mineralization.

Results

UDCA significantly decreased cell survival at concentrations 10 times higher (1 mM) than that observed with LCA, whereas CA did not decrease osteoblast survival. UDCA (100 μM) neutralized the damaging effects of bilirubin (50 μM) and sera from jaundiced patients on survival. Moreover, UDCA (1 μM and 10 μM) increased osteoblast differentiation in cells treated with harmful concentrations of LCA or bilirubin. UDCA (100 μM) increased cell differentiation in osteoblasts cultured with a mix of serum from cholestatic patients by 23%. Furthermore, UDCA increased osteoblast mineralization by 35% and neutralized the negative consequences of 50 μM bilirubin.

Conclusions

UDCA increases osteoblast differentiation and mineralization, and neutralizes the detrimental effects of lithocholic acid, bilirubin and sera from jaundiced patients on osteoblastic cells. Therefore, UDCA may exert a favourable effect on bone in patients which chronic cholestasis.

Ancillary