Overexpression of programmed cell death ligand 1 reduces LPS-induced inflammatory cytokine upregulation and enhances osteo/odontogenic-differentiation of human dental pulp stem cells via upregulation of CCCTC-binding factor

IF 2.2 4区医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE

Archives of oral biology Pub Date : 2024-06-13 DOI:10.1016/j.archoralbio.2024.106031

Yinan Zhu , Minmin Chen , Fang Liu , Buyun Li , Yanwen He

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Abstract

Objective

The aim of this study was to explore the effect and mechanism of programmed cell death ligand 1 (PD-L1) in promoting the proliferation and osteo/odontogenic-differentiation of human dental pulp stem cells (hDPSCs) by mediating CCCTC-binding factor (CTCF) expression.

Design

The interaction between PD-L1 and CTCF was verified through co-immunoprecipitation. hDPSCs transfected with PD-L1 overexpression and CTCF knockdown vectors were treated with lipopolysaccharide or an osteogenic-inducing medium. Inflammatory cytokines and osteo/odontogenic-differentiation related genes were measured. Osteo/odontogenic-differentiation of hDPSCs was assessed using alkaline phosphatase (ALP) and alizarin red S staining.

Results

Overexpression of PD-L1 inhibited LPS-induced pro-inflammatory cytokine upregulation, cell proliferation, ALP activity, and calcium deposition in hDPSCs and elevated the expression of osteo/odontogenic-differentiation related genes; however, such expression patterns could be reversed by CTCF knockdown. Co-immunoprecipitation results confirmed the binding of PD-L1 to CTCF, indicating that PD-L1 overexpression in hDPSCs increases CTCF expression, thus inhibiting the inflammatory response and increasing osteo/odontogenic-differentiation of hDPSCs.

Conclusion

PD-L1 overexpression in hDPSCs enhances the proliferation and osteo/odontogenic-differentiation of hDPSCs and inhibit the inflammatory response by upregulating CTCF expression.

Abstract Image

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过表达程序性细胞死亡配体 1 可降低 LPS 诱导的炎性细胞因子上调，并通过上调 CCCTC 结合因子增强人牙髓干细胞的成骨/成牙分化能力

目的本研究旨在探讨程序性细胞死亡配体1（PD-L1）通过介导CCCTC结合因子（CTCF）的表达促进人牙髓干细胞（hDPSCs）增殖和成骨/成牙分化的作用和机制。用脂多糖或成骨诱导培养基处理转染了PD-L1过表达和CTCF敲除载体的hDPSC。对炎性细胞因子和骨/牙生成分化相关基因进行了测定。结果PD-L1的过表达抑制了LPS诱导的促炎细胞因子上调、细胞增殖、ALP活性和hDPSCs中的钙沉积，并提高了成骨/成牙分化相关基因的表达；然而，这种表达模式可被CTCF敲除逆转。共免疫沉淀结果证实了 PD-L1 与 CTCF 的结合，表明在 hDPSCs 中过表达 PD-L1 会增加 CTCF 的表达，从而抑制炎症反应并增加 hDPSCs 的成骨/成牙分化。

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来源期刊

Archives of oral biology 医学-牙科与口腔外科

CiteScore

5.10

自引率

3.30%

发文量

177

审稿时长

26 days

期刊介绍： Archives of Oral Biology is an international journal which aims to publish papers of the highest scientific quality in the oral and craniofacial sciences. The journal is particularly interested in research which advances knowledge in the mechanisms of craniofacial development and disease, including: Cell and molecular biology Molecular genetics Immunology Pathogenesis Cellular microbiology Embryology Syndromology Forensic dentistry

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