TWIST, a basic helix-loop-helix transcription factor, can regulate the human osteogenic lineage

Basic helix-loop-helix (bHLH) transcription factors have been shown to play an important role in controlling cell type determination and differentiati on. 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 exp ression of sense and antisense TWIST in human osteoblast HSaOS-2 cells. Cha nges in morphology and osteogenic phenotype characterized these stable clon es. Cells that overexpressed TWIST exhibited a spindle shaped morphology, r educed levels of alkaline phosphatase, a reduced proliferation rate, and fa iled to respond to basic fibroblast growth factor (bFGF). In contrast, thos e that underexpressed TWIST demonstrated a cuboidal epithelial-like morphol ogy characteristic of differentiated osteoblasts. TWIST antisense cells exh ibited increased levels of alkaline phosphatase and type I collagen mRNA, i nitiated osteopontin mRNA expression, and had a reduced proliferation rate. These results indicate that TWIST overexpressing cells may de-differentiat e and remain in an osteoprogenitor-like state, and antisense TWIST cells pr ogress to a more differentiated mature osteoblast-like state. Therefore, th e level of TWIST can influence osteogenic gene expression and may act as a master switch in initiating bone cell differentiation by regulating the ost eogenic cell lineage. (C) 1999 Wiley-Liss, Inc.