title: Wnt16 is involved in intramembranous ossification and suppresses osteoblast differentiation through the Wnt/β-catenin pathway.
abstract: In the course of embryonic development skeletal elements form either through intramembranous or endochondral ossification. Wnt proteins play diverse roles during vertebrate skeletal development. Wnt16 is a key factor in developing long bones, but its exact role in craniofacial bone formation remains unclear. This study was initially undertaken to investigate the expression of Wnt16 during craniofacial bone development in mouse embryos. Wnt16 expression in the osteoid of calvaria, maxilla, and mandible started later than that of ALP and osteocalcin (OCN), but before mineralization of the craniofacial bones, suggesting that Wnt16 is involved in intramembranous ossification in the head. To confirm this, MC3T3-E1 cells were transfected with an adenovirus containing Wnt16 (Ad-Wnt16). Ad-Wnt16 cells showed decreased ALP activity and less mineralized nodule formations compared with control cells. In addition, the mRNA levels of osteogenic markers were reduced. Moreover, Wnt16 activated β-catenin signaling in MC3T3-E1 cells at both transcription and protein levels as shown by a TOPflash luciferase reporter gene assay and western blot analysis. On the other hand, Wnt/β-catenin pathway blockade by Dickkopf 1 abrogated the suppression of mineralization by Wnt16. Our findings suggest that Wnt16 is involved in intramembranous ossification and suppresses osteoblast differentiation through the Wnt/β-catenin pathway.
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, P.R. China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Jiang
authors.forename: Johannes W
authors.initials: JW
authors.lastname: Von den Hoff
authors.forename: Ruurd
authors.initials: R
authors.lastname: Torensma
authors.forename: Liuyan
authors.initials: L
authors.lastname: Meng
authors.forename: Zhuan
authors.initials: Z
authors.lastname: Bian
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D018507:Gene Expression Regulation, Developmental; D005822:Genetic Vectors; D005865:Gestational Age; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008334:Mandible / Q000196:embryology / Q000378:metabolism; D008437:Maxilla / Q000196:embryology / Q000378:metabolism; D051379:Mice; D010006:Osteoblasts / Q000378:metabolism*; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D010012:Osteogenesis; D012886:Skull / Q000196:embryology / Q000378:metabolism*; D051820:TCF Transcription Factors / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: C495267:CTNNB1 protein, mouse; C501127:Dkk1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D051820:TCF Transcription Factors; D051153:Wnt Proteins; C585687:Wnt16 protein, mouse; D051176:beta Catenin; D015675:Osteocalcin; D000469:Alkaline Phosphatase