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牙周炎胱硫醚γ-裂解酶缺陷型小鼠 M1 巨噬细胞功能减弱和骨吸收。

Weakening of M1 macrophage and bone resorption in periodontitis cystathionine γ-lyase-deficient mice.

机构信息

Department of Orthodontics, Stomatological Hospital and Dental School of Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai, China.

出版信息

Oral Dis. 2024 Mar;30(2):769-779. doi: 10.1111/odi.14374. Epub 2022 Sep 27.

DOI:10.1111/odi.14374
PMID:36097830
Abstract

OBJECTIVES

Cystathionine-γ-lyase (CTH) has been proved to involve in inflammation and bone remolding, implying its potential role in the progression of periodontitis. This study was aimed to investigate the function of CTH and its relation to the macrophage polarization in periodontitis.

MATERIALS AND METHODS

Bone marrow-derived macrophages (BMDMs) from wild-type (WT) and Cth knockout (Cth ) mice were stimulated with lipopolysaccharide (LPS) in vitro and pro-inflammatory cytokines were analyzed by qRT-PCR. Ligature-induced periodontitis was established on WT and Cth mice. Histological analysis, tartrate-resistant acid phosphatase staining, immunostaining, and Western blot were performed to analyze the periodontium destruction and M1 macrophage polarization.

RESULTS

Cth expression in BMDMs was upregulated upon increasing LPS stimulation. Deletion of Cth suppressed BMDMs inflammatory response with decreased Il1b, Il6, and Tnf mRNA. Cth mice with periodontitis showed attenuated bone loss and impaired osteoclast differentiation compared with WT. Moreover, Cth knockout hindered M1 macrophage polarization, reduced the expression of IL-1β, IL-6, and TNF-α in periodontally diseased tissue.

CONCLUSION

This study demonstrated that CTH played an important role in regulating the inflammatory responses and periodontitis tissue destruction. Importantly, Cth knockout suppressed M1 macrophages polarization in periodontitis.

摘要

目的

胱硫醚-γ-裂解酶(CTH)已被证明参与炎症和骨重塑,这意味着其在牙周炎进展中具有潜在作用。本研究旨在探讨 CTH 的功能及其与牙周炎中巨噬细胞极化的关系。

材料和方法

体外用脂多糖(LPS)刺激野生型(WT)和 Cth 敲除(Cth)小鼠的骨髓来源巨噬细胞(BMDMs),并用 qRT-PCR 分析促炎细胞因子。在 WT 和 Cth 小鼠上建立结扎诱导的牙周炎。进行组织学分析、抗酒石酸酸性磷酸酶染色、免疫染色和 Western blot,以分析牙周破坏和 M1 巨噬细胞极化。

结果

LPS 刺激时 BMDMs 中的 Cth 表达上调。Cth 缺失抑制了 BMDMs 的炎症反应,导致 Il1b、Il6 和 Tnf mRNA 减少。与 WT 相比,患有牙周炎的 Cth 敲除小鼠表现出骨丢失减少和破骨细胞分化受损。此外,Cth 敲除抑制了 M1 巨噬细胞极化,减少了牙周病组织中 IL-1β、IL-6 和 TNF-α的表达。

结论

本研究表明 CTH 在调节炎症反应和牙周炎组织破坏中起重要作用。重要的是,Cth 敲除抑制了牙周炎中的 M1 巨噬细胞极化。

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