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

Abstract

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. 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. 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. UDCA significantly decreased cell survival at concentrations 10 times higher (1mM) than that observed with LCA, whereas CA did not decrease osteoblast survival. UDCA (100μM) neutralized the damaging effects of bilirubin (50μM) and sera from jaundiced patients on survival. Moreover, UDCA (1μM and 10μM) increased osteoblast differentiation in cells treated with harmful concentrations of LCA or bilirubin. UDCA (100μM) 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 50μM bilirubin. 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.