Human Dermo-1 has attributes similar to twist in early bone development.
Basic helix-loop-helix (bHLH) transcription factors are implicated in cell lineage determination and differentiation. Dermo-1 encodes a bHLH transcription factor that shares extensive homology with another bHLH transcription factor, Twist. We have cloned and characterized human Dermo-1 from two different bone cytoplasmic DNA (cDNA) libraries. Dermo-1 mRNA and protein expression were examined in human embryo and adult tissue sections. Dermo-1 is expressed in a subset of mesodermally and ectodermally derived tissues. We further examined expression of Dermo-1/Twist in human tissues and cell lines. In addition, we observed Dermo-1 expression in response to basic fibroblast growth factor in osteoblastic cell lines. To evaluate the functionality of the human Dermo-1 transcription factor in osteoblast metabolism, we made stable osteoblastic cell lines that over- and underexpress human Dermo-1. These cell lines were analyzed and compared with previously published data of similar cell lines transfected with Twist. Our results demonstrate that Dermo-1 caused changes similar to Twist in the osteogenic properties of osteoblastic cells, such as morphology, bone marker gene expression, and biochemical response to cytokines. However, Dermo-1 expression also has unique effects in regulating the mechanism of proliferation, on alkaline phosphatase enzyme activity, and in temporal expression patterns. We speculate that expression of Twist and Dermo-1 maintains cells in an osteoprogenitor or preosteoblast-like state, respectively, and prevents premature or ectopic osteoblast differentiation. Therefore, Twist and Dermo-1 must be sequentially downregulated in order to initiate the cascade of events responsible for osteogenic cell differentiation. These results indicate that, during osteoblast development, Dermo-1 may inhibit osteoblast maturation and maintain cells in a preosteoblast phenotype by utilizing mechanisms similar but not identical to those utilized by Twist.
Lee
M S
MS
Division of Molecular Medicine, Beckman Research Institute of the City of Hope, Duarte, CA 91010-3011, USA.
Lowe
G
G
Flanagan
S
S
Kuchler
K
K
Glackin
C A
CA
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001846:Bone Development / Q000502:physiology*; D002460:Cell Line; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000378:metabolism; D051766:Early Growth Response Protein 1; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D017874:Immediate-Early Proteins; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D012097:Repressor Proteins; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D051879:Twist-Related Protein 1
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D017874:Immediate-Early Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; C103173:TWIST1 protein, human; C486274:TWIST2 protein, human; D014157:Transcription Factors; D051879:Twist-Related Protein 1; C096852:Twist2 protein, mouse; D016222:Fibroblast Growth Factor 2