title: The transcription factor DLX3 regulates the osteogenic differentiation of human dental follicle precursor cells.
abstract: The transcription factor DLX3 plays a decisive role in bone development of vertebrates. In neural-crest derived stem cells from the dental follicle (DFCs), DLX3 is differentially expressed during osteogenic differentiation, while other osteogenic transcription factors such as DLX5 or RUNX2 are not highly induced. DLX3 has therefore a decisive role in the differentiation of DFCs, but its actual biological effects and regulation are unknown. This study investigated the DLX3-regulated processes in DFCs. After DLX3 overexpression, DFCs acquired a spindle-like cell shape with reorganized actin filaments. Here, marker genes for cell morphology, proliferation, apoptosis, and osteogenic differentiation were significantly regulated as shown in a microarray analysis. Further experiments showed that DFCs viability is directly influenced by the expression of DLX3, for example, the amount of apoptotic cells was increased after DLX3 silencing. This transcription factor stimulates the osteogenic differentiation of DFCs and regulates the BMP/SMAD1-pathway. Interestingly, BMP2 did highly induce DLX3 and reverse the inhibitory effect of DLX3 silencing in osteogenic differentiation. However, after DLX3 overexpression in DFCs, a BMP2 supplementation did not improve the expression of DLX3 and the osteogenic differentiation. In conclusion, DLX3 influences cell viability and regulates osteogenic differentiation of DFCs via a BMP2-dependent pathway and a feedback control.
authors: Department of Oral and Maxillofacial Surgery, University of Regensburg, Regensburg, Germany.
authors: Sandra
authors: S
authors: Viale-Bouroncle
authors: Oliver
authors: O
authors: Felthaus
authors: Gottfried
authors: G
authors: Schmalz
authors: Gero
authors: G
authors: Brockhoff
authors: Torsten E
authors: TE
authors: Reichert
authors: Christian
authors: C
authors: Morsczeck
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D002454:Cell Differentiation; D049109:Cell Proliferation; D048430:Cell Shape; D002470:Cell Survival; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D003795:Dental Sac / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation; D020868:Gene Silencing; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008964:Molar, Third / Q000166:cytology; D020411:Oligonucleotide Array Sequence Analysis; D010012:Osteogenesis; D010957:Plasmids / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051898:Smad1 Protein / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: C525718:BMP2 protein, human; D015415:Biomarkers; D055396:Bone Morphogenetic Protein 2; C088334:Distal-less homeobox proteins; D018398:Homeodomain Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C497399:SMAD1 protein, human; D051898:Smad1 Protein; D014157:Transcription Factors