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

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)...

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Main Authors: ZHANG Bin, NI Zhenhong, YANG Peng, KUANG Liang, OUYANG Junjie
Format: Article
Language:zho
Published: Editorial Office of Journal of Third Military Medical University 2019-04-01
Series:Di-san junyi daxue xuebao
Subjects:
Online Access:http://aammt.tmmu.edu.cn/Upload/rhtml/201901091.htm
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author ZHANG Bin
NI Zhenhong
YANG Peng
KUANG Liang
OUYANG Junjie
author_facet ZHANG Bin
NI Zhenhong
YANG Peng
KUANG Liang
OUYANG Junjie
author_sort ZHANG Bin
collection DOAJ
description 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 (P < 0.05), decreased the proportion of M1 macrophages and upregulated the proportion of M2 macrophages in the synovium (P < 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 (P < 0.05). LIPUS also decreased the protein levels of p-JNK and p-NF-κB p65 in LPS-stimulated macrophages (P < 0.05) and suppressed LPS-induced nuclear translocation of NF-κB (P < 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.
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spelling doaj.art-533dceff48574ae59818854756c1e60a2022-12-22T04:07:53ZzhoEditorial Office of Journal of Third Military Medical UniversityDi-san junyi daxue xuebao1000-54042019-04-0141874775610.16016/j.1000-5404.201901091Low-intensity pulsed ultrasound suppresses synovitis by modulating polarization of synovial macrophages in mice with osteoarthritisZHANG Bin0NI Zhenhong1YANG Peng2KUANG Liang3OUYANG Junjie4State 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, ChinaState 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, ChinaState 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, ChinaState 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, ChinaState 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, ChinaObjective 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 (P < 0.05), decreased the proportion of M1 macrophages and upregulated the proportion of M2 macrophages in the synovium (P < 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 (P < 0.05). LIPUS also decreased the protein levels of p-JNK and p-NF-κB p65 in LPS-stimulated macrophages (P < 0.05) and suppressed LPS-induced nuclear translocation of NF-κB (P < 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.http://aammt.tmmu.edu.cn/Upload/rhtml/201901091.htmlow-intensity pulsed ultrasoundosteoarthritismacrophagespolarization
spellingShingle ZHANG Bin
NI Zhenhong
YANG Peng
KUANG Liang
OUYANG Junjie
Low-intensity pulsed ultrasound suppresses synovitis by modulating polarization of synovial macrophages in mice with osteoarthritis
Di-san junyi daxue xuebao
low-intensity pulsed ultrasound
osteoarthritis
macrophages
polarization
title Low-intensity pulsed ultrasound suppresses synovitis by modulating polarization of synovial macrophages in mice with osteoarthritis
title_full Low-intensity pulsed ultrasound suppresses synovitis by modulating polarization of synovial macrophages in mice with osteoarthritis
title_fullStr Low-intensity pulsed ultrasound suppresses synovitis by modulating polarization of synovial macrophages in mice with osteoarthritis
title_full_unstemmed Low-intensity pulsed ultrasound suppresses synovitis by modulating polarization of synovial macrophages in mice with osteoarthritis
title_short Low-intensity pulsed ultrasound suppresses synovitis by modulating polarization of synovial macrophages in mice with osteoarthritis
title_sort low intensity pulsed ultrasound suppresses synovitis by modulating polarization of synovial macrophages in mice with osteoarthritis
topic low-intensity pulsed ultrasound
osteoarthritis
macrophages
polarization
url http://aammt.tmmu.edu.cn/Upload/rhtml/201901091.htm
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AT nizhenhong lowintensitypulsedultrasoundsuppressessynovitisbymodulatingpolarizationofsynovialmacrophagesinmicewithosteoarthritis
AT yangpeng lowintensitypulsedultrasoundsuppressessynovitisbymodulatingpolarizationofsynovialmacrophagesinmicewithosteoarthritis
AT kuangliang lowintensitypulsedultrasoundsuppressessynovitisbymodulatingpolarizationofsynovialmacrophagesinmicewithosteoarthritis
AT ouyangjunjie lowintensitypulsedultrasoundsuppressessynovitisbymodulatingpolarizationofsynovialmacrophagesinmicewithosteoarthritis