Absence of estrogen receptor-related-alpha increases osteoblastic differentiation and cancellous bone mineral density.

Abstract:

:The nuclear orphan receptor human estrogen receptor-related receptor (ERR)-alpha is implicated in bone metabolism. We studied the effect of ERRalpha silencing in human mesenchymal stem cells (hMSCs) during osteoblastogenesis. We found that ERRalpha silencing led to an increase of bone sialoprotein and a decrease of osteopontin mRNA levels, suggesting enhanced osteoblastic differentiation. This was confirmed by an increased ability of hMSCs to deposit calcium. Concomitantly, knockdown of ERRalpha inhibited adipogenesis, resulting in a decrease in adipocyte number and adipocyte marker gene expression. In line with a negative role of ERRalpha in bone metabolism, we found that adult female and male ERRalpha-deficient mice displayed a moderate increase in femoral cancellous bone volume and density. Osteoblast surface was increased and marrow fat volume decreased in these animals. Furthermore, ERRalpha-deficient osteoblasts displayed increased differentiation properties in vitro in line with our observations in hMSCs. In summary, we identified a role for ERRalpha in bone mass regulation by affecting osteoblastic differentiation.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Delhon I,Gutzwiller S,Morvan F,Rangwala S,Wyder L,Evans G,Studer A,Kneissel M,Fournier B

doi

10.1210/en.2009-0121

subject

Has Abstract

pub_date

2009-10-01 00:00:00

pages

4463-72

issue

10

eissn

0013-7227

issn

1945-7170

pii

en.2009-0121

journal_volume

150

pub_type

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