title: Nuclear factor I-C reciprocally regulates adipocyte and osteoblast differentiationviacontrol of canonical Wnt signaling.
abstract: Nuclear factor I-C (NFIC) has recently been identified as an important player in osteogenesis and bone homeostasisin vivoHowever, the molecular mechanisms involved have yet to be defined. In the current study, Nfic expression was altered in primary marrow stromal cells and established progenitor lines after adipogenic and osteogenic treatment. Overexpression of Nfic in stromal cells ST2, mesenchymal cells C3H10T1/2, and primary marrow stromal cells inhibited adipogenic differentiation, whereas it promoted osteogenic differentiation. Conversely, silencing of endogenous Nfic in the cell lines enhanced adipogenic differentiation, whereas it blocked osteogenic differentiation. Mechanism investigations revealed that Nfic overexpression promoted nuclear translocation of β-catenin and increased nuclear protein levels of β-catenin and transcription factor 7-like 2 (TCF7L2). Promoter studies and the chromatin immunoprecipitation (ChIP) assay revealed that NFIC directly binds to the promoter of low-density lipoprotein receptor-related protein 5 (Lrp5) and thereafter transactivates the promoter. Finally, inactivation of canonical Wnt signaling in ST2 attenuated the inhibition of adipogenic differentiation and stimulation of osteogenic differentiation by NFIC. Our study suggests that NFIC balances adipogenic and osteogenic differentiation from progenitor cells through controlling canonical Wnt signaling and highlights the potential of NFIC as a target for new therapies to control metabolic disorders like osteoporosis and obesity.-Zhou, J., Wang, S., Qi, Q., Yang, X., Zhu, E., Yuan, H., Li, X., Liu, Y., Li, X., Wang, B. Nuclear factor I-C reciprocally regulates adipocyte and osteoblast differentiationviacontrol of canonical Wnt signaling.
authors.affiliation: Key Laboratory of Hormones and Development, Ministry of Health, Tianjin Key Laboratory of Metabolic Diseases, Metabolic Diseases Hospital and Institute of Endocrinology, Tianjin Medical University, Tianjin, China.|2011 Collaborative Innovation Center for Metabolic Diseases, Metabolic Diseases Hospital, Tianjin Medical University, Tianjin, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.affiliation: College of Basic Medical Sciences, Tianjin Medical University, Tianjin, China; and.
authors.forename: Shan
authors.initials: S
authors.lastname: Wang
authors.affiliation: Key Laboratory of Hormones and Development, Ministry of Health, Tianjin Key Laboratory of Metabolic Diseases, Metabolic Diseases Hospital and Institute of Endocrinology, Tianjin Medical University, Tianjin, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Qi
authors.affiliation: Stomatological Hospital, Tianjin Medical University, Tianjin, China.
authors.forename: Xiaoyue
authors.initials: X
authors.lastname: Yang
authors.affiliation: Key Laboratory of Hormones and Development, Ministry of Health, Tianjin Key Laboratory of Metabolic Diseases, Metabolic Diseases Hospital and Institute of Endocrinology, Tianjin Medical University, Tianjin, China.
authors.forename: Endong
authors.initials: E
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Hormones and Development, Ministry of Health, Tianjin Key Laboratory of Metabolic Diseases, Metabolic Diseases Hospital and Institute of Endocrinology, Tianjin Medical University, Tianjin, China.
authors.forename: Hairui
authors.initials: H
authors.lastname: Yuan
authors.affiliation: Key Laboratory of Hormones and Development, Ministry of Health, Tianjin Key Laboratory of Metabolic Diseases, Metabolic Diseases Hospital and Institute of Endocrinology, Tianjin Medical University, Tianjin, China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Li
authors.affiliation: Stomatological Hospital, Tianjin Medical University, Tianjin, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: College of Basic Medical Sciences, Tianjin Medical University, Tianjin, China; and.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Li
authors.affiliation: Key Laboratory of Hormones and Development, Ministry of Health, Tianjin Key Laboratory of Metabolic Diseases, Metabolic Diseases Hospital and Institute of Endocrinology, Tianjin Medical University, Tianjin, China; blwang@tmu.edu.cn.|2011 Collaborative Innovation Center for Metabolic Diseases, Metabolic Diseases Hospital, Tianjin Medical University, Tianjin, China.
authors.forename: Baoli
authors.initials: B
authors.lastname: Wang
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D050156:Adipogenesis / Q000502:physiology; D000818:Animals; D001842:Bone and Bones / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D059630:Mesenchymal Stem Cells / Q000166:cytology; D008810:Mice, Inbred C57BL; D051839:NFI Transcription Factors / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology*; D010012:Osteogenesis / Q000502:physiology*; D013234:Stem Cells / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000502:physiology*; D051176:beta Catenin / Q000378:metabolism
chemical_list: C495267:CTNNB1 protein, mouse; D051839:NFI Transcription Factors; D051153:Wnt Proteins; D051176:beta Catenin
keywords:  adipogenesis; Lrp5; Wnt/β-catenin; osteogenesis