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M2 巨噬细胞来源的外泌体通过促进 CXCL12 的表达促进人牙周膜干细胞的成骨分化并抑制其炎症反应。

M2 macrophage-derived exosomes enable osteogenic differentiation and inhibit inflammation in human periodontal ligament stem cells through promotion of CXCL12 expression.

机构信息

Department of Stomatology, Fuyang Cancer Hospital, Fuyang, Anhui, China.

Department of Stomatology, The First Affiliated Hospital of Bengbu Medical University, No.287, Changhuai Road, Bengbu, Anhui, 233000, China.

出版信息

BMC Oral Health. 2024 Sep 11;24(1):1070. doi: 10.1186/s12903-024-04831-4.

Abstract

BACKGROUND

Periodontitis is a dental disease characterized by inflammation of periodontal tissues and loss of the periodontal ligaments and alveolar bone. Exosomes are a class of extracellular vesicles that are involved in a variety of diseases by releasing active substances. In this study, we aimed to investigate the effect and mechanism of exosomes from M2 polarized macrophages (M2-exos) on osteogenic differentiation in human periodontal ligament stem cells (hPDLSCs).

METHODS

M2-exos were isolated from IL-4-induced RAW264.7 cells (M2 macrophages) and then treated on hPDLSCs. Osteogenic differentiation was assessed by alkaline phosphatase (ALP) staining, alizarin red S (ARS) staining, measurement of osteogenic differentiation-related genes and proteins, and inflammation was evaluated by measuring the levels of inflammatory factors. The mechanism of M2-exo was confirmed through qPCR, western blot, ALP and ARS staining.

RESULTS

Results suggested that M2-exo improved osteogenic differentiation and inhibited inflammation in LPS-induced hPDLSCs. CXCL12 expression was elevated in M2 macrophages, but decreased in LPS-induced hPDLSCs. Moreover, the effect of M2-exo on osteogenic differentiation and inflammation in LPS-induced hPDLSCs was reversed by CXCL12 knockdown.

CONCLUSION

We demonstrated that M2-exo facilitated osteogenic differentiation and suppressed inflammation in LPS-induced hPDLSCs through promotion of CXCL12 expression. These results suggested the potential of M2-exo in the treatment of periodontitis, which may provide a new theoretical basis for M2-exo treatment of periodontitis.

摘要

背景

牙周炎是一种以牙周组织炎症和牙周韧带及牙槽骨丧失为特征的牙科疾病。外泌体是一类细胞外囊泡,通过释放活性物质参与多种疾病的发生。在本研究中,我们旨在探讨 M2 极化巨噬细胞来源的外泌体(M2-exos)对人牙周膜干细胞(hPDLSCs)成骨分化的影响及其机制。

方法

从 IL-4 诱导的 RAW264.7 细胞(M2 巨噬细胞)中分离 M2-exos,然后作用于 hPDLSCs。通过碱性磷酸酶(ALP)染色、茜素红 S(ARS)染色、检测成骨分化相关基因和蛋白,评估成骨分化;通过测量炎症因子的水平,评估炎症。通过 qPCR、western blot、ALP 和 ARS 染色,验证 M2-exo 的作用机制。

结果

结果表明,M2-exo 可改善 LPS 诱导的 hPDLSCs 中的成骨分化并抑制炎症。M2 巨噬细胞中 CXCL12 表达上调,而 LPS 诱导的 hPDLSCs 中表达下调。此外,CXCL12 敲低可逆转 M2-exo 对 LPS 诱导的 hPDLSCs 中成骨分化和炎症的影响。

结论

我们证明,M2-exo 通过促进 CXCL12 表达促进 LPS 诱导的 hPDLSCs 中的成骨分化并抑制炎症。这些结果表明 M2-exo 在治疗牙周炎方面具有潜力,可能为 M2-exo 治疗牙周炎提供新的理论依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8637/11391719/ced6244af897/12903_2024_4831_Fig1_HTML.jpg

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