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Zic1 transcription factor in bone: neural developmental protein regulates mechanotransduction in osteocytes

Lookup NU author(s): Emeritus Professor Roger Francis, Dr Mark Birch, Dr Harish Datta


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A transcriptome analysis compared gene expression in human bone biopsy samples taken from lumbar spine and iliac crest, sites that experience high and low levels of mechanical stress, respectively. The analysis revealed that the zinc finger protein of cerebellum (Zic) family member transcription factor Zic1 was the most up-regulated gene in the lumbar spine (202-fold; P<10−7) in comparison with the iliac crest. Software analysis of differential gene expression in the biopsy samples identified the ciliary-related proteins PATCH1 and GLI-Kruppel family members Gli1 and Gli3 as part of a potential molecular network associated with Zic1. RT-PCR confirmed the expression of Zic1, Gli1, and Gli3 and other related key signaling mediators in osteoblastic cells and osteocytes in vitro. Zic1 was immunolocalized in the cytosol and nucleus of the murine osteocyte cell line MLO-Y4 and osteoblast-like cells MC3T3-E1 and in primary rat osteoblasts. MLO-Y4 cells subjected to prolonged oscillatory fluid flow showed increased localization of Zic1 in the nucleus with diminished levels in the cytosol, but no such changes were seen in MC3T3-E1 cells. A shear stress-induced increase in T-cell factor/lymphoid enhancer factor transcriptional activity was abolished by Zic1 gene silencing. These results suggest that Zic1, perhaps together with Gli1 and Gli3, may act as a link between mechanosensing and Wnt signaling. We conclude that Zic1, a neural developmental transcription factor, plays an important role in shear flow mechanotransduction in osteocytes.

Publication metadata

Author(s): Kalogeropoulos M, Varanasi SS, Olstad OK, Sanderson P, Gautvik VT, Reppe S, Francis RM, Gautvik KM, Birch MA, Datta HK

Publication type: Article

Publication status: Published

Journal: FASEB Journal

Year: 2010

Volume: 24

Issue: 8

Pages: 2893-2903

Print publication date: 30/03/2010

ISSN (print): 0892-6638

ISSN (electronic): 1530-6860

Publisher: Federation of American Societies for Experimental Biology


DOI: 10.1096/fj.09-148908


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Funder referenceFunder name
Newcastle University
FP6-502491European Union