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.

High expression of KIF3A is a potential new parameter for the diagnosis and prognosis of breast cancer

“…KIF3A was also reported to be associated with certain pathological processes. It has been reported that KIF3A is involved in forming defective bone formation and osteopenia ( 13 ) and defective osteoblastic differentiation in dental mesenchymal stem/precursor cells ( 14 ). Since 2013, the expression and function of KIF3A has been regarded as statistically significantly and correlated with several tumors such as glioblastoma, prostate cancer and medulloblastoma ( 4 , 5 , 10 ).…”

Decreased Expression of Cilia Genes in Pancreatic Islets as a Risk Factor for Type 2 Diabetes in Mice and Humans

“…Because many central cilia genes, such as Aurka, the aurora kinase A gene, are also directly implicated in proliferation (Fu et al, 2007), we had to identify a candidate that was, rather, involved in cilia organization. We selected Kif3a, encoding the kinesin family member 3A, which has been documented as a key factor in ciliogenesis and the intraflagellar transport of primary cilia (Jiang et al, 2016;Rosenbaum and Witman, 2002). Murine Kif3a expression was significantly less in NZO, as compared with B6-ob/ob, islets ( Figure 6A, left), and KIF3A protein tended to be decreased after high glucose treatment ( Figure 6A, right).…”

Effects of graphene oxide and graphene oxide quantum dots on the osteogenic differentiation of stem cells from human exfoliated deciduous teeth

“…It is usually known that the Wnt/b-catenin pathway plays an important role in homeostasis and osteogenesis [54,55]. Jiang S et al [56] reported that SHEDs could differentiate into osteoblasts and odontoblasts and suppress the adipogenic differentiation through Wnt signaling pathways. Results from Western blot were in agreement with the results from qRT-PCR.…”