ERRα regulates osteoblastic and adipogenic differentiation of mouse bone marrow mesenchymal stem cells

The orphan nuclear receptor estrogen-related receptor-alpha (ERR alpha) has been reported to have both a positive and a negative regulatory role in osteoblastic and adipocytic differentiation. We have studied the role of ERR alpha in osteoblastic and adipogenic differentiation of mesenchymal stem cells. Bone marrow mesenchymal stem cells were isolated from ERR alpha deficient mice and their differentiation capacities were compared to that of the wild-type cells. ERR alpha deficient cultures displayed reduced cellular proliferation, osteoblastic differentiation, and mineralization. In the complementary experiment, overexpression of ERR alpha in MC3T3-E1 cells increased the expression of osteoblastic markers and mineralization. Alterations in the expression of bone sialoprotein (BSP) may at least partially explain the effects on mineralization as BSP expression was reduced in ERR alpha deficient MSCs and enhanced upon ERR alpha overexpression in MC3T3-E1 cells. Furthermore, a luciferase reporter construct driven by the BSP promoter was efficiently transactivated by ERR alpha. Under adipogenic conditions, ERR alpha deficient cultures displayed reduced adipocytic differentiation. Our data thus propose a positive role for ERR alpha in osteoblastic and adipocytic differentiation. The variability in the results yielded in the different studies implies that ERR alpha may play different roles in bone under different physiological conditions. (C) 2010 Elsevier Inc. All rights reserved.