title: Down-regulation of Wnt10a affects odontogenesis and proliferation in mesenchymal cells.
abstract: The WNT10a mutation has been found in patients with abnormal odontogenesis. In mice, Wnt10a expression is found in the tooth germ, but its role has not yet been elucidated. We aimed to investigate the role of Wnt10a in odontogenesis. Mesenchymal cells of the first mandibular molar germ at the bell stage were isolated, transfected with Wnt10a SiRNA or plasmid, and reassociated with epithelial part of the molar germ. Scrambled SiRNA or empty vector was used in the control group. The reassociated tooth germs were transplanted into mice subrenal capsules. After gene modification, dental mesenchymal cells cultured in vitro were checked for cell proliferation and the expression of Dspp was examined. All 12 reassociated tooth germs in the control group resumed odontogenesis, while only 5 of 12 in the Wnt10a knockdown group developed into teeth. After Wnt10a knockdown, the mesenchymal cells cultured in vitro presented repressed proliferation. Wnt10a knockdown and overexpression led to both down- and up-regulation of Dspp. We conclude that the down-regulation of Wnt10a impairs odontogensis and cell proliferation, and that Wnt10a regulates Dspp expression in mesenchymal cells. These findings help to elucidate the mechanism of abnormal tooth development in patients with the WNT10A mutation.
authors.affiliation: Department of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, PR China. Ly10160624@163.com
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Dong
authors.initials: D
authors.lastname: Han
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Hailan
authors.initials: H
authors.lastname: Feng
mesh_terms: D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation; D002478:Cells, Cultured; D015536:Down-Regulation; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006651:Histocytochemistry; D008297:Male; D008648:Mesoderm / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D008963:Molar / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009805:Odontogenesis / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012795:Sialoglycoproteins / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014083:Tooth Germ / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D051153:Wnt Proteins / Q000235:genetics* / Q000378:metabolism; D000099311:Dentin Sialophosphoprotein
chemical_list: D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D012795:Sialoglycoproteins; D051153:Wnt Proteins; D000099311:Dentin Sialophosphoprotein; C484143:Wnt10a protein, mouse