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TWIST , a basic helix‐loop‐helix transcription factor, can regulate the human osteogenic lineage
Author(s) -
Lee MinSeob,
Lowe Gi.,
Strong Donna D.,
Wergedal Jon E.,
Glackin Carlotta A.
Publication year - 1999
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/(sici)1097-4644(19991215)75:4<566::aid-jcb3>3.0.co;2-0
Subject(s) - basic helix loop helix , osteopontin , osteoblast , microbiology and biotechnology , transcription factor , alkaline phosphatase , basic fibroblast growth factor , twist , biology , cellular differentiation , fibroblast growth factor , runx2 , twist transcription factor , type i collagen , growth factor , gene , genetics , endocrinology , biochemistry , dna binding protein , in vitro , enzyme , receptor , geometry , mathematics , nuclear protein
Basic helix‐loop‐helix (bHLH) transcription factors have been shown to play an important role in controlling cell type determination and differentiation. TWIST, a member of the bHLH transcription factor family, is involved in the development of mesodermally derived tissue, including the skeleton. We examined the role of human TWIST in osteoblast metabolism using stable expression of sense and antisense TWIST in human osteoblast HSaOS‐2 cells. Changes in morphology and osteogenic phenotype characterized these stable clones. Cells that overexpressed TWIST exhibited a spindle shaped morphology, reduced levels of alkaline phosphatase, a reduced proliferation rate, and failed to respond to basic fibroblast growth factor (bFGF). In contrast, those that underexpressed TWIST demonstrated a cuboidal epithelial‐like morphology characteristic of differentiated osteoblasts. TWIST antisense cells exhibited increased levels of alkaline phosphatase and type I collagen mRNA, initiated osteopontin mRNA expression, and had a reduced proliferation rate. These results indicate that TWIST overexpressing cells may de‐differentiate and remain in an osteoprogenitor‐like state, and antisense TWIST cells progress to a more differentiated mature osteoblast‐like state. Therefore, the level of TWIST can influence osteogenic gene expression and may act as a master switch in initiating bone cell differentiation by regulating the osteogenic cell lineage. J. Cell. Biochem. 75:566–577, 1999. © 1999 Wiley‐Liss, Inc.