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Oncostatin M regulates macrophages polarization in osseointegration via yes-associated protein
International Immunopharmacology ( IF 5.6 ) Pub Date : 2023-05-21 , DOI: 10.1016/j.intimp.2023.110348
Ying Yuan 1 , Qin Zhang 2 , Bingfeng Wu 3 , Tianyu Huang 3 , Ping Gong 2 , Lin Xiang 2
Affiliation  

Objectives

Oncostatin M(OSM), secreted by monocytes and macrophages, has been noted to participate in bone homeostasis and macrophage polarization, which might be regulated by yes-associated protein (YAP). This study aimed to elucidate the influence and mechanisms of OSM-YAP on macrophages polarization in osseointegration.

Material and methods

In vitro, flow cytometry, real-time PCR, and Elisa were performed to evaluate inflammatory function in bone marrow-derived macrophages (BMDMs) with OSM, siOSMR, and YAP inhibitor verteporfin (VP). In vivo, macrophage-specific YAP-deficient mice were generated to investigate the role of OSM via YAP signaling in osseointegration.

Results

This study demonstrated that OSM could inhibit the M1 polarization, promote the M2 polarization, and induce the expression of osteogenic-related factors via VP. The conditional knock-out of YAP inhibited the osseointegration in mice, and promoted the inflammatory reaction around the implants, while OSM could restore the effect.

Conclusions

Our results demonstrated that OSM might play an important role in the polarization of BMDMs, and bone formation around dental and femoral implants. This effect was closely conducted by Hippo-YAP pathway.

Clinical Significance

Understanding the role and mechanism of OSM in macrophage polarization around dental implants could improve comprehension of signal network of osseointegration, and it might offer a potential target of therapies to accelerate osseointegration and reduce inflammatory reactions.



中文翻译:

制瘤素 M 通过 yes 相关蛋白调节骨整合中的巨噬细胞极化

目标

单核细胞和巨噬细胞分泌的制瘤素 M(OSM) 参与骨稳态和巨噬细胞极化,这可能受到 yes 相关蛋白 (YAP) 的调节。本研究旨在阐明OSM-YAP对骨整合中巨噬细胞极化的影响和机制。

材料与方法

在体外,通过流式细胞术、实时 PCR 和 Elisa 评估 OSM、siOSMR 和 YAP 抑制剂维替泊芬 (VP) 的骨髓源性巨噬细胞 (BMDM) 的炎症功能。在体内,产生巨噬细胞特异性 YAP 缺陷小鼠,以研究 OSM 通过 YAP 信号传导在骨整合中的作用。

结果

本研究证明OSM可以抑制M1极化,促进M2极化,并通过VP诱导成骨相关因子的表达。条件性敲除YAP会抑制小鼠的骨整合,并促进种植体周围的炎症反应,而OSM则可以恢复这种效果。

结论

我们的结果表明,OSM 可能在 BMDM 的极化以及牙科和股骨植入物周围的骨形成中发挥重要作用。这种效应是由Hippo-YAP通路紧密传导的。

临床意义

了解OSM在牙种植体周围巨噬细胞极化中的作用和机制可以提高对骨整合信号网络的理解,并且可能为加速骨整合和减少炎症反应的治疗提供潜在的靶标。

更新日期:2023-05-22
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