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Nuclear factor I‐C reciprocally regulates adipocyte and osteoblast differentiation via control of canonical Wnt signaling
Author(s) -
Zhou Jie,
Wang Shan,
Qi Qi,
Yang Xiaoyue,
Zhu Endong,
Yuan Hairui,
Li Xuemei,
Liu Ying,
Li Xiaoxia,
Wang Baoli
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201600975rr
Subject(s) - wnt signaling pathway , adipocyte , osteoblast , microbiology and biotechnology , chemistry , endocrinology , medicine , non canonical , signal transduction , biology , biochemistry , adipose tissue , in vitro
Nuclear factor I‐C (NFIC) has recently been identified as an important player in osteogenesis and bone homeostasis in vivo. However, 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 differentiation via control of canonical Wnt signaling. FASEB J. 31, 1939–1952 (2017). www.fasebj.org