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Stem Cells. 2014 Sep;32(9):2467-79. doi: 10.1002/stem.1733.

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

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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.


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-C controls 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.


Adipogenesis; Bone marrow stromal cells; Differentiation; Osteoblast; Osteoporosis; Proliferation

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