Zic1 transcription factor in bone: neural developmental protein regulates mechanotransduction in osteocytes
| Autor: | Roger M. Francis, Harish K. Datta, S S Varanasi, Sjur Reppe, Kaare M. Gautvik, Michail Kalogeropoulos, Vigdis T. Gautvik, Paul Sanderson, Mark A. Birch, Ole Kristoffer Olstad |
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| Rok vydání: | 2010 |
| Předmět: |
musculoskeletal diseases
Pathology medicine.medical_specialty Kruppel-Like Transcription Factors Nerve Tissue Proteins Biology Mechanotransduction Cellular Osteocytes Zinc Finger Protein GLI1 Biochemistry ZIC1 Iliac crest Bone and Bones Cell Line Mice Zinc Finger Protein Gli3 Gene expression GLI3 Genetics medicine Animals Cilia Mechanotransduction Molecular Biology Transcription factor Zinc finger Gene Expression Profiling Rats Cell biology medicine.anatomical_structure Osteocyte Stress Mechanical Transcription Factors Biotechnology |
| Zdroj: | The FASEB Journal. 24:2893-2903 |
| ISSN: | 1530-6860 0892-6638 |
| Popis: | 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; P10(-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. |
| Databáze: | OpenAIRE |
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