Home » Key Stem Cells Research Articles » NFI-C regulates osteoblast differentiation via control of osterix expression.

NFI-C regulates osteoblast differentiation via control of osterix expression.

Lee DS, Choung HW, Kim HJ, Gronostajski RM, Yang YI, Ryoo HM, Lee ZH, Kim HH, Cho ES, Park JC.

Stem Cells. 2014 Sep;32(9):2467-79.

Department of Oral Histology-Developmental Biology, Seoul National University, Chongro-gu, Seoul, Korea; Department of Anatomy and Orofacial Development, School of Dentistry, Chosun University, Dong-gu, Gwangju, Korea.

 

Abstract

 

In bone marrow, bone marrow stromal cells (BMSCs) have the capacity to differentiate into osteoblasts and adipocytes. Age-related osteoporosis is associated with a reciprocal decrease of osteogenesis and an increase of adipogenesis in bone marrow. In this study, we demonstrate that disruption of nuclear factor I-C (NFI-C) impairs osteoblast differentiation and bone formation, and increases bone marrow adipocytes. Interestingly, NFI-Ccontrols postnatal bone formation but does not influence prenatal bone development. We also found decreased NFI-C expression in osteogenic cells from human osteoporotic patients. Notably, transplantation of Nfic-overexpressing BMSCs stimulates osteoblast differentiation and new bone formation, but inhibits adipocyte differentiation by suppressing peroxisome proliferator-activated receptor gamma expression in Nfic(-/-) mice showing an age-related osteoporosis-like phenotype. Finally, NFI-C directly regulates Osterix expression but acts downstream of the bone morphogenetic protein-2-Runx2 pathway. These results suggest that NFI-C acts as a transcriptional switch in cell fate determination between osteoblast and adipocyte differentiation in BMSCs. Therefore, regulation of NFI-C expression in BMSCs could be a novel therapeutic approach for treating age-related osteoporosis.

© 2014 AlphaMed Press.

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bone marrow stromal cells