The FASEB journal, 2017-05, Vol.31 (5), p.1939-1952
2017
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- Autor(en) / Beteiligte
- Titel
- Nuclear factor I‐C reciprocally regulates adipocyte and osteoblast differentiation via control of canonical Wnt signaling
- Ist Teil von
- The FASEB journal, 2017-05, Vol.31 (5), p.1939-1952
- Ort / Verlag
- United States: Federation of American Societies for Experimental Biology
- Erscheinungsjahr
- 2017
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- ABSTRACT 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
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0892-6638eISSN: 1530-6860DOI: 10.1096/fj.201600975RRTitel-ID: cdi_proquest_miscellaneous_1897369946
- Format
- –
- Schlagworte
- Adipocytes, Adipocytes - metabolism, adipogenesis, Adipogenesis - physiology, Animals, beta Catenin - metabolism, Biocompatibility, Biomedical materials, Bone and Bones - metabolism, Bone turnover, Cell Differentiation - physiology, Cell lines, Cells (biology), Cells, Cultured, Chromatin, Deactivation, Differentiation, Heparan sulfate, Homeostasis, Immunoprecipitation, Inactivation, Lrp5, LRP5 protein, Mesenchymal Stromal Cells - cytology, Mesenchyme, Metabolic disorders, Mice, Inbred C57BL, Molecular modelling, NFI Transcription Factors - metabolism, Nuclear factor I, Nuclear transport, Osteoblastogenesis, Osteoblasts - cytology, Osteogenesis, Osteogenesis - physiology, Osteoporosis, Osteoprogenitor cells, Receptor density, Signaling, Stem Cells - metabolism, Stromal cells, Stromal Cells - metabolism, Translocation, Wnt protein, Wnt Proteins - metabolism, Wnt Signaling Pathway - physiology, Wnt/β‐catenin, β-Catenin