title: Ursodeoxycholic acid increases differentiation and mineralization and neutralizes the damaging effects of bilirubin on osteoblastic cells.
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Centro de Investigación Biomédica en Red, University of Barcelona, Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Dubreuil
authors.forename: Silvia
authors.initials: S
authors.lastname: Ruiz-Gaspà
authors.forename: Nuria
authors.initials: N
authors.lastname: Guañabens
authors.forename: Pilar
authors.initials: P
authors.lastname: Peris
authors.forename: Luisa
authors.initials: L
authors.lastname: Alvarez
authors.forename: Ana
authors.initials: A
authors.lastname: Monegal
authors.forename: Andrés
authors.initials: A
authors.lastname: Combalia
authors.forename: Albert
authors.initials: A
authors.lastname: Parés
mesh_terms: D001663:Bilirubin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002113:Calcification, Physiologic / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002779:Cholestasis / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D007565:Jaundice / Q000097:blood; D008095:Lithocholic Acid / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects; D010024:Osteoporosis / Q000209:etiology* / Q000378:metabolism*; D018709:Statistics, Nonparametric; D014580:Ursodeoxycholic Acid / Q000494:pharmacology*
chemical_list: D008095:Lithocholic Acid; D014580:Ursodeoxycholic Acid; D001663:Bilirubin
keywords: bile acids; bone mass; cholestasis; osteoporosis; primary biliary cirrhosis