Dentin-derived BMP-2 and odontoblast differentiation.
It is known that stem cells from exfoliated deciduous teeth (SHED) can be induced to differentiate into odontoblasts. However, the nature of dentin-derived morphogenic signals required for dental pulp stem cell differentiation remains unclear. The hypothesis underlying this work is that dentin-derived Bone Morphogenetic Proteins (BMP) are necessary for the differentiation of SHED into odontoblasts. We observed that SHED express markers of odontoblastic differentiation (DSPP, DMP-1, MEPE) when seeded in human tooth slice/scaffolds and cultured in vitro, or implanted subcutaneously into immunodeficient mice. In contrast, SHED cultured in deproteinized tooth slice/scaffolds, or scaffolds without a tooth slice, do not express these markers. SHED express the BMP receptors BMPR-IA, BMPR-IB, and BMPR-II. Notably, blockade of BMP-2 signaling inhibited the expression of markers of odontoblastic differentiation by SHED cultured in tooth slice/scaffolds. Collectively, this work demonstrates that dentin-derived BMP-2 is required to induce the differentiation of SHED into odontoblasts.
Casagrande
L
L
Department of Pediatric Dentistry, School of Dentistry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
Demarco
F F
FF
Zhang
Z
Z
Araujo
F B
FB
Shi
S
S
Nör
J E
JE
D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D015415:Biomarkers / Q000032:analysis; D015153:Blotting, Western; D055396:Bone Morphogenetic Protein 2 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D055419:Bone Morphogenetic Protein 7 / Q000037:antagonists & inhibitors / Q000494:pharmacology; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000032:analysis; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000032:analysis; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003782:Dental Pulp / Q000166:cytology; D003804:Dentin / Q000201:enzymology*; D016326:Extracellular Matrix Proteins / Q000032:analysis; D006023:Glycoproteins / Q000032:analysis; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009804:Odontoblasts / Q000187:drug effects*; D010750:Phosphoproteins / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012795:Sialoglycoproteins / Q000032:analysis; D015398:Signal Transduction / Q000187:drug effects; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology; D040521:Subcutaneous Tissue / Q000601:surgery; D054457:Tissue Scaffolds; D014094:Tooth, Deciduous / Q000166:cytology; D000099311:Dentin Sialophosphoprotein
D057134:Antibodies, Neutralizing; D015415:Biomarkers; D055396:Bone Morphogenetic Protein 2; D055419:Bone Morphogenetic Protein 7; D052005:Bone Morphogenetic Protein Receptors, Type I; D052006:Bone Morphogenetic Protein Receptors, Type II; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D010750:Phosphoproteins; D012795:Sialoglycoproteins; D000099311:Dentin Sialophosphoprotein; C525718:BMP2 protein, human; C525819:BMP7 protein, human; C513309:DMP1 protein, human; C486579:MEPE protein, human; C498211:BMPR1A protein, human; C498214:BMPR1B protein, human; C498218:BMPR2 protein, human