Targeted disruption of nuclear factor erythroid-derived 2-like 1 in osteoblasts reduces bone size and bone formation in mice.

Abstract:

:Previous in vitro studies found that nuclear factor erythroid-derived 2-like 1 (NFE2L1) was involved in mediating ascorbic acid-induced osterix expression and osteoblast differentiation via binding to the antioxidant response element of the osterix promoter. To test the role of NFE2L1 in regulating bone formation in vivo, we disrupted NFE2L1 specifically in osteoblasts. Mice expressing Cre under the control of Col1alpha2 promoter were crossed with NFE2L1 loxP mice to generate Cre+ knockout (KO) and Cre- wild-type (WT) mice. Skeletal measurements by DEXA revealed 8-10% and 9-11% reduction in total body BMC and bone area in the KO mice from 3 to 8 wk of age. Peripheral quantitative computed tomography analyses found both periosteal and endosteal circumferences were reduced by 6% at the middiaphysis of the femurs from 8 wk old KO mice. Histomorphometric analyses revealed reduced bone formation was a cause for reduced bone size in the KO mice. Microcomputed tomography analysis of the metaphysis of the femur revealed that trabecular bone volume/total volume, and trabecular numbers were decreased by 30 and 53% in the NFE2L1 KO mice. Expression of osterix was decreased by 57% in the bones of NFE2L1 KO mice. In vitro nodule assay demonstrated that mineralized nodule area was reduced by 68% in the cultures of bone marrow stromal cells from NFE2L1 KO mice. Treatment of primary osteoblasts with ascorbic acid increased osterix expression by fourfold, whereas loss of NFE2L1 in osteoblasts diminished ascorbic acid stimulation of osterix expression by 50%. Our data provide the first in vivo experimental evidence that NFE2L1 produced by osteoblasts is involved in regulating osterix expression, osteoblast differentiation, and bone formation.

journal_name

Physiol Genomics

journal_title

Physiological genomics

authors

Kim J,Xing W,Wergedal J,Chan JY,Mohan S

doi

10.1152/physiolgenomics.00105.2009

subject

Has Abstract

pub_date

2010-01-08 00:00:00

pages

100-10

issue

2

eissn

1094-8341

issn

1531-2267

pii

00105.2009

journal_volume

40

pub_type

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