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This Article Accepted manuscript (PDF) All Versions of this Article: JOE-08-0514v1 201/2/263    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Zanotti, S. Articles by Canalis, E. Search for Related Content PubMed PubMed Citation Articles by Zanotti, S. Articles by Canalis, E.

S Zanotti, Research, St Francis Hospital and Medical Center, Hartford, United States
L Stadmeyer, Research, St Francis Hospital and Medical Center, Hartford, United States
A Smerdel-Ramoya, Research, St Francis Hospital and Medical Center, Hartford, United States
D Durant, Research, St Francis Hospital and Medical Center, Hartford, United States
E Canalis, Research, St Francis Hospital and Medical Center, Hartford, United States

Correspondence: Ernesto Canalis, Email: ecanalis{at}stfranciscare.org

Abstract

CCAAT/Enhancer Binding Proteins (C/EBPs) are expressed by osteoblasts and adipocytes during differentiation. C/EBPb is critical for adipogenesis; however its role in osteoblastogenesis is unclear, and its function in the postnatal skeleton is not known. To study C/EBPb in osteoblasts in vivo, we created transgenic mice expressing full length C/EBPb under the control of a 3.8 kilobase fragment of the human osteocalcin promoter. Two transgenic lines were established in an FVB genetic background, and compared to wild type littermate controls. Both C/EBP transgenic lines exhibited osteopenia, with a 30% decrease in bone volume, due to a decrease in trabecular number. The number of osteoblasts and osteoclasts per bone perimeter was not changed. Bone marrow stromal cells from C/EBP transgenics showed reduced mineralization, and reduced alkaline phosphatase mRNA levels. Calvarial osteoblasts from C/EBPb transgenics displayed reduced alkaline phosphatase activity. To determine the consequences of the Cebpb deletion in vivo, the phenotype of Cebpb null mice was compared to that of wild type controls of identical genetic composition. Cebpb null mice exhibited reduced weight, body fat, and bone mineral density, and decreased bone volume, due to a decrease in trabecular number. The number of osteoblasts and osteoclasts per bone perimeter was not changed. C/EBPb down regulation by RNA interference in calvarial osteoblasts had no effect on osteoblast differentiation/function. The phenotype of the Cebpb inactivation may be secondary to systemic indirect effects, and to direct effects of C/EBPb in osteoblasts. In conclusion, C/EBPb plays a role in mesenchymal cell differentiation and its misexpression in vivo causes osteopenia.