CKIP-1 suppresses odontoblastic differentiation of dental pulp stem cells via BMP2 pathway and can interact with NRP1
Yihua Song1, Chenfei Wang1, Zhifeng Gu2
1a Department of Stomatology , Affiliated Hospital of Nantong University, Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University , Nantong , Jiangsu , China.
Aim:
Casein kinase 2 interacting protein-1 (CKIP-1) is a recently discovered intracellular regulator of bone formation, muscle cell differentiation, and tumor cell proliferation. Our study aims to identify the inhibition of BMP2-Smad1/5 signaling by CKIP-1 in odontoblastic differentiation of human dental pulp stem cells (DPSCs).
Materials And Methods:
DPSCs infected CKIP-1 siRNA or transfected CKIP-1 full-length plasmid were cultured in odontoblastic differentiation medium or added noggin (200 ng/mL) for 21 days. We examined the effects of CKIP-1 on odontoblastic differentiation, mineralized nodules formation, and interaction by western blot, real-time polymerase chain reaction (RT-PCR), alkaline phosphatase (ALP) staining, alizarin red S staining, and immunoprecipitation.
Results:
Firstly, we have demonstrated that CKIP-1 expression markedly decreased time-dependently along with cell odontoblastic differentiation. Indeed, the silence of CKIP-1 upregulated odontoblastic differentiation via BMP2-Smad1/5 signaling, while CKIP-1 over-expression had a negative effect on odontoblastic differentiation of DPSCs. Furthermore, CKIP-1 could interact with Neuropilin-1 (NRP1).
Conclusions:
This work provides data that advocates a novel perception on odontoblastic differentiation of DPSCs. Therefore, inhibiting the expression of CKIP-1 may be of great significance to the development of dental caries.
Insights
Casein kinase 2 interacting protein-1 (CKIP-1) inhibits odontoblastic differentiation in human dental pulp stem cells (DPSCs). Inhibiting CKIP-1 promotes differentiation via BMP2-Smad1/5 signaling, suggesting therapeutic potential for dental caries.
Area of Science:
- Biomedical Science
- Stem Cell Biology
- Regenerative Dentistry
Background:
- Casein kinase 2 interacting protein-1 (CKIP-1) is an intracellular regulator involved in bone formation and cell differentiation.
- Odontoblastic differentiation is crucial for dentin regeneration and maintaining dental health.
Purpose of the Study:
- To investigate the role of CKIP-1 in the odontoblastic differentiation of human dental pulp stem cells (DPSCs).
- To elucidate the mechanism by which CKIP-1 regulates BMP2-Smad1/5 signaling during this process.
Main Methods:
- DPSCs were treated with CKIP-1 siRNA or a full-length plasmid.
- Cells were cultured in odontoblastic differentiation medium with or without noggin.
- Techniques included western blot, RT-PCR, ALP staining, alizarin red S staining, and immunoprecipitation.
Main Results:
- CKIP-1 expression decreased during odontoblastic differentiation.
- CKIP-1 inhibition upregulated odontoblastic differentiation via BMP2-Smad1/5 signaling.
- CKIP-1 overexpression inhibited differentiation and interacted with Neuropilin-1 (NRP1).
Conclusions:
- CKIP-1 negatively regulates odontoblastic differentiation in DPSCs.
- Inhibiting CKIP-1 may offer a novel therapeutic strategy for dental caries treatment.
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