title: Disruption of kif3a results in defective osteoblastic differentiation in dental mesenchymal stem/precursor cells via the Wnt signaling pathway.
abstract: The anterograde intraflagellar transport motor protein, kif3a, regulates the integrity of primary cilia and various cellular functions, however, the role of kif3a in dental mesenchymal stem/precursor cell differentiation remains to be fully elucidated. In the present study, the expression of kif3a was knocked down in human dental follicle cells (hDFCs) and human dental pulp cells (hDPCs) using short hairpin RNA. The results of subsequent immunofluorescence revealed that knocking down kif3a resulted in the loss of primary cilia, which led to impairment of substantial mineralization and expression of the differentiation‑associated markers, including alkaline phosphatase, Runt‑related transcription factor 2, dentin matrix protein 1 and dentin sialophosphoprotein in the hDFCs and hDPCs. The results of reverse transcription‑quantitative polymerase chain reaction and western blot analyses showed that the expression levels of Wnt3a‑mediated active β‑catenin and lymphoid enhancer‑binding factor 1 were attenuated, whereas the expression of phosphorylated glycogen synthase kinase 3β was enhanced, in the kif3a‑knockdown cells. In addition, exogenous Wnt3a partially rescued osteoblastic differentiation in the hDFCs and hDPCs. These results demonstrated that inhibition of kif3a in the hDFCs and hDPCs disrupted primary cilia formation and/or function, and indicated that kif3a is important in the differentiation of hDFCs and hDPCs through the Wnt pathway. These findings not only enhance current understanding of tooth development and diseases of tooth mineralization, but also indicate possible strategies to regulate mineralization during tooth repair and regeneration.
authors.affiliation: School of Life Sciences and Key Laboratory of Bio‑Resources and Eco‑Environment, Ministry of Education, Sichuan University, Chengdu, Sichuan 610064, P.R. China.
authors.forename: Sicong
authors.initials: S
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Lian
authors.initials: L
authors.lastname: Feng
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Zongting
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Mei
authors.initials: M
authors.lastname: Yu
authors.affiliation: School of Life Sciences and Key Laboratory of Bio‑Resources and Eco‑Environment, Ministry of Education, Sichuan University, Chengdu, Sichuan 610064, P.R. China.
authors.forename: Jinku
authors.initials: J
authors.lastname: Bao
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Tian
mesh_terms: D000293:Adolescent; D002454:Cell Differentiation; D002478:Cells, Cultured; D003782:Dental Pulp / Q000166:cytology* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D016547:Kinesins / Q000502:physiology*; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000502:physiology; D009805:Odontogenesis; D010006:Osteoblasts; D060449:Wnt Signaling Pathway
chemical_list: C087415:KIF3A protein, human; D016547:Kinesins