Slug gene expression supports human osteoblast maturation.
This study aims to define the function of Slug transcription factor in human normal osteoblasts (hOBs). To date, Slug is considered exclusively a marker of malignancy in bone tissue. Here, we identified, for the first time, a role for Slug in hOBs using a knockdown approach. We demonstrated that Slug is positively correlated with osteoblast markers, including Runx2, osteopontin, osteocalcin, Collagen type 1, Wnt/beta-catenin signaling mediators, and mineral deposition. At the same time, Slug silencing potentiates the expression of Sox-9, a factor indispensable for chondrogenic development. These data, with the finding that Slug is in vivo recruited by the promoters of Runx2 and Sox-9 genes, suggest that, in hOBs, Slug may act both as positive and negative transcriptional regulator of Runx2 and Sox-9 genes, respectively. In summary, our results support the hypothesis that Slug functions as a novel regulator of osteoblast activity and may be considered a new factor required for osteoblast maturation.
Lambertini
Elisabetta
E
Department of Biochemistry and Molecular Biology, Molecular Biology Section, University of Ferrara, Via Fossato di Mortara, 74, 44100, Ferrara, Italy.
Lisignoli
Gina
G
Torreggiani
Elena
E
Manferdini
Cristina
C
Gabusi
Elena
E
Franceschetti
Tiziana
T
Penolazzi
Letizia
L
Gambari
Roberto
R
Facchini
Andrea
A
Piva
Roberta
R
D000368:Aged; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology; D055785:Gene Knockdown Techniques; D006801:Humans; D008875:Middle Aged; D010006:Osteoblasts / Q000378:metabolism / Q000502:physiology*; D010012:Osteogenesis / Q000235:genetics / Q000502:physiology; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D051153:Wnt Proteins / Q000502:physiology
D050659:Core Binding Factor Alpha 1 Subunit; C493709:RUNX2 protein, human; C000604407:SNAI1 protein, human; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D051153:Wnt Proteins