title: NFI-C regulates osteoblast differentiation via control of osterix expression.
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-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.
authors.affiliation: 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.
authors.forename: Dong-Seol
authors.initials: DS
authors.lastname: Lee
authors.forename: Han-Wool
authors.initials: HW
authors.lastname: Choung
authors.forename: Heung-Joong
authors.initials: HJ
authors.lastname: Kim
authors.forename: Richard M
authors.initials: RM
authors.lastname: Gronostajski
authors.forename: Young-Il
authors.initials: YI
authors.lastname: Yang
authors.forename: Hyun-Mo
authors.initials: HM
authors.lastname: Ryoo
authors.forename: Zang Hee
authors.initials: ZH
authors.lastname: Lee
authors.forename: Hong-Hee
authors.initials: HH
authors.lastname: Kim
authors.forename: Eui-Sic
authors.initials: ES
authors.lastname: Cho
authors.forename: Joo-Cheol
authors.initials: JC
authors.lastname: Park
mesh_terms: D000368:Aged; D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000502:physiology; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D051839:NFI Transcription Factors / Q000235:genetics / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism*; D010012:Osteogenesis / Q000502:physiology; D000076182:Sp7 Transcription Factor; D014157:Transcription Factors / Q000096:biosynthesis*; D014162:Transfection
chemical_list: D051839:NFI Transcription Factors; C497647:NFIC protein, human; C497648:Nfic protein, mouse; D000076182:Sp7 Transcription Factor; C479466:Sp7 protein, mouse; D014157:Transcription Factors
keywords: Adipogenesis; Bone marrow stromal cells; Differentiation; Osteoblast; Osteoporosis; Proliferation