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微/纳米结构氧化锆表面通过减少炎症条件下的细胞焦亡促进人骨髓间充质干细胞的成骨分化。

Micro-/nano-structured zirconia surface promotes osteogenic differentiation of human bone marrow mesenchymal stem cells by reducing pyroptosis under inflammatory conditions.

作者信息

Wang Hui-Min, Ding Qian, Chen Ying, Zhang Yao-Jun, Wu Zhi-Xiao, Zhang Xiao, Zhang Lei

机构信息

Department of Prosthodontics, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology & Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health & NMPA Key Laboratory for Dental Materials, Beijing, China.

出版信息

J Dent Sci. 2025 Jul;20(3):1422-1435. doi: 10.1016/j.jds.2025.02.012. Epub 2025 Feb 20.

Abstract

BACKGROUND/PURPOSE: Promoting osteogenesis under inflammatory conditions holds promise for preventing and mitigating peri-implantitis. Cell pyroptosis inhibits osteoblast-mediated bone formation. Although the surface topography of implant materials influences both osteogenesis and inflammatory responses, its effects on pyroptosis and osteogenesis under inflammatory conditions have not been thoroughly investigated. The aim of this study was to investigate the effects of a porous and hydrofluoric acid-etched micro-/nano-structured zirconia (POROHF) surface on pyroptosis and osteogenesis of human bone marrow mesenchymal stem cells (hBMSCs) under inflammatory conditions.

MATERIALS AND METHODS

Lipopolysaccharide (LPS) and adenosine 5'-triphosphate (ATP) were used to induce pyroptosis in hBMSCs and evaluate the effects of pyroptosis on osteogenesis of hBMSCs. Then, using commonly used sandblasted acid-etched titanium and zirconia surfaces as controls, the effects of POROHF surface on pyroptosis and osteogenesis under inflammatory conditions simulated by LPS and ATP were evaluated. To clarify the potential mechanisms by which the surface affected pyroptosis of hBMSCs, RNA sequencing and functional verification were also performed.

RESULTS

LPS and ATP induced caspase-1/GSDMD-mediated pyroptosis in hBMSCs and thereby inhibited osteogenic differentiation and angiogenic potential of hBMSCs, which could be partially reversed by inhibiting pyroptosis. The POROHF surface could reduce pyroptosis levels, thereby promoting osteogenesis of hBMSCs under inflammatory conditions. The surface reduced pyroptosis of hBMSCs by downregulating expression and upregulating expression.

CONCLUSION

This study highlighted the inhibitory effects of caspase-1/GSDMD-mediated pyroptosis on osteogenesis of hBMSCs and demonstrated that micro-/nano-structured zirconia surface could promote osteogenic differentiation of hBMSCs by reducing pyroptosis under inflammatory conditions.

摘要

背景/目的:在炎症条件下促进骨生成有望预防和减轻种植体周围炎。细胞焦亡会抑制成骨细胞介导的骨形成。尽管种植体材料的表面形貌会影响骨生成和炎症反应,但其在炎症条件下对焦亡和骨生成的影响尚未得到充分研究。本研究的目的是探讨多孔且经氢氟酸蚀刻的微/纳米结构氧化锆(POROHF)表面在炎症条件下对人骨髓间充质干细胞(hBMSCs)焦亡和骨生成的影响。

材料与方法

使用脂多糖(LPS)和三磷酸腺苷(ATP)诱导hBMSCs发生焦亡,并评估焦亡对hBMSCs骨生成的影响。然后,以常用的喷砂酸蚀钛和氧化锆表面作为对照,评估POROHF表面在由LPS和ATP模拟的炎症条件下对焦亡和骨生成的影响。为阐明该表面影响hBMSCs焦亡的潜在机制,还进行了RNA测序和功能验证。

结果

LPS和ATP诱导hBMSCs发生半胱天冬酶-1/ Gasdermin D介导的焦亡,从而抑制hBMSCs的成骨分化和血管生成潜能,抑制焦亡可部分逆转这种情况。POROHF表面可降低焦亡水平,从而在炎症条件下促进hBMSCs的骨生成。该表面通过下调 表达和上调 表达来减少hBMSCs的焦亡。

结论

本研究突出了半胱天冬酶-1/ Gasdermin D介导的焦亡对hBMSCs骨生成的抑制作用,并证明微/纳米结构氧化锆表面可通过在炎症条件下减少焦亡来促进hBMSCs的成骨分化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b357/12254821/753e831bb154/gr1.jpg

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本文引用的文献

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Role and Mechanism of a Micro-/Nano-Structured Porous Zirconia Surface in Regulating the Biological Behavior of Bone Marrow Mesenchymal Stem Cells.
ACS Appl Mater Interfaces. 2023 Mar 22;15(11):14019-14032. doi: 10.1021/acsami.2c22736. Epub 2023 Mar 13.
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Osteogenic and anti-inflammatory effects of SLA titanium substrates doped with chitosan-stabilized selenium nanoparticles via a covalent coupling strategy.
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