Low-intensity pulsed ultrasound suppresses synovitis by modulating polarization of synovial macrophages in mice with osteoarthritis

Bin ZHANG; Zhenhong NI; Peng YANG; Liang KUANG; Junjie OUYANG; Yangli XIE; Wanling JIANG; Mi LIU; Xiaolan DU; Lin CHEN

doi:10.16016/j.1000-5404.201901091

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Low-intensity pulsed ultrasound suppresses synovitis by modulating polarization of synovial macrophages in mice with osteoarthritis

更新时间：2026-03-02

- Low-intensity pulsed ultrasound suppresses synovitis by modulating polarization of synovial macrophages in mice with osteoarthritis
- Journal of Third Military Medical University Vol. 41, Issue 8, Pages: 747-756(2019)
- 作者机构：
  
  400042 重庆，陆军军医大学(第三军医大学)野战外科研究所：创伤、烧伤与复合伤国家重点实验室，创伤实验室，战创伤康复研究室，骨代谢与修复中心State Key Laboratory of Trauma, Burns and Combined Injury, Labratory of Trauma, Department of Rehabilitation Medicine for War Injuries, Center of Bone Metabolism and Repair, Institute of Surgery Research, Army Medical University (Third Military Medical University), Chongqing, 400042, China
- 作者简介：
- 基金信息：
  
  the Key Program of National Natural Science Foundation of China(81530071);the Key Project of Innovation Program in Military Medicine(16CXZ016)
- DOI：10.16016/j.1000-5404.201901091
  CLC： R-332;R454.3;R684.3
- Received：11 January 2019，
  
  Published：30 April 2019
- 稿件说明：
移动端阅览
Bin ZHANG, Zhenhong NI, Peng YANG, et al. Low-intensity pulsed ultrasound suppresses synovitis by modulating polarization of synovial macrophages in mice with osteoarthritis[J]. Journal of Third Military Medical University, 2019, 41(8): 747-756.
DOI：

Bin ZHANG, Zhenhong NI, Peng YANG, et al. Low-intensity pulsed ultrasound suppresses synovitis by modulating polarization of synovial macrophages in mice with osteoarthritis[J]. Journal of Third Military Medical University, 2019, 41(8): 747-756. DOI： 10.16016/j.1000-5404.201901091.

摘要

目的

探讨低强度脉冲超声(low-intensity pulsed ultrasound，LIPUS)抑制关节滑膜炎的作用和可能机制。

方法

采用小鼠内侧半月板不稳定(destabilization of medial meniscus，DMM)关节炎模型。21只小鼠按随机数字表法分为3组：对照组、DMM组和DMM+LIPUS组。组织学分析各组膝关节滑膜病理改变，统计滑膜中iNOS或CD206阳性细胞占F4/80阳性巨噬细胞的比例。将体外培养的THP-1细胞系分为对照组、LIPUS组、LPS(lipopolysaccharide)组和LPS+LIPUS组，将Raw 264.7细胞分为LPS组和LPS+LIPUS组。采用荧光定量PCR技术检测IL-1β、TNF-α、IL-10和精氨酸酶1(Arg1)等巨噬细胞极化相关基因的表达

Western blot检测p-JNK和p-NF-κB p65蛋白表达水平；激光共聚焦显微镜观察THP-1细胞NF-κBp65核转位状态。

结果

在DMM关节炎模型中，LIPUS处理后的小鼠滑膜的厚度比未处理组变薄(

0.05)，滑膜中M1型巨噬细胞比例减少(

0.05)，M2型巨噬细胞比例增加(

0.05)；在LPS诱导的炎症条件下，LIPUS处理抑制THP-1和Raw 264.7细胞的M1型巨噬细胞相关基因的表达，同时促进M2型巨噬细胞相关基因的表达，抑制了p-JNK和p-NF-κB p65的蛋白表达水平(

0.05)，LIPUS抑制THP-1细胞NF-κB p65的核转位(

0.05)。

结论

LIPUS可以缓解关节滑膜炎，该作用可能与JNK和NF-κB通路介导的滑膜巨噬细胞极化有关。

Abstract

Objective

To investigate the therapeutic effect of low-intensity pulsed ultrasound (LIPUS) on synovitis in a mouse model of osteoarthritis and explore the possible mechanism.

Methods

We assessed the therapeutic effect of LIPUS on synovitis in a mouse model of destabilization of medial meniscus (DMM). The histopathology of the synovium of the knee joint was examined in 7 mice with DMM (model group)

7 normal mice (control group) and 7 mice with DMM treated with LIPUS. The proportion of iNOS- and CD206-positive cells in F4/80-positive macrophages in the synovium was detected. Cultured THP-1 macrophages were divided into control group

LIPUS group

lipopolysaccharide (LPS) group and LPS+LIPUS group

and Raw 264.7 cells were divided into LPS group and LPS+LIPUS group with corresponding treatments. The mRNA levels of polarization-related indexes (IL-1β

TNF-α

IL-10 and Arg1) were detected using real-time quantitative PCR after the treatments

and the protein levels of p-JNK and p-NF-κB p65 were detected using Western blotting. Confocal laser scanning microscopy was used to observe the nuclear translocation of nuclear factor-κB (NF-κB) in THP-1 cells after LPS or LPS+LIPUS treatment.

Results

In the mouse models of DMM

treatment with LIPUS significantly reduced the thicknesses of the synovium (

0.05)

decreased the proportion of M1 macrophages and upregulated the proportion of M2 macrophages in the synovium (

0.05). In THP-1 and Raw 264.7 macrophages stimulated with LPS

LIPUS treatment significantly lowered IL-1β and TNF-α levels but increased IL-10 and Arg1 levels (

0.05). LIPUS also decreased the protein levels of p-JNK and p-NF-κB p65 in LPS-stimulated macrophages (

0.05) and suppressed LPS-induced nuclear translocation of NF-κB (

0.05).

Conclusion

LIPUS produces anti-inflammatory effects on the synovium in the mouse model of osteoarthritis possibly by modulating the polarization of synovial macrophages through the JNK and NF-κB signaling pathways.

关键词

Keywords

references

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