Effects of adenovirus-mediated knockdown of IRAK4 on synovitis in the osteoarthritis rabbit model

Abstract Background The use of interleukin-1 receptor-associated kinase 4 (IRAK4) inhibitor as a treatment for the inflammatory joint disease is a promising method. However, its underlying mechanism in osteoarthritis (OA) remains unclear. The purpose of this study is to look into the effects of aden...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Muzhe Li, Huiyun Li, Xun Ran, Han Yin, Xuling Luo, Zhiwei Chen
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Interleukin-1 receptor-associated kinase 4 Synovitis Osteoarthritis Toll-like receptor/IL-1 receptor Inflammation Diseases of the musculoskeletal system RC925-935
Acceso en línea:	https://doaj.org/article/ca00de771fcc430db4ae7f2cef703102
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:ca00de771fcc430db4ae7f2cef703102
record_format	dspace
spelling	oai:doaj.org-article:ca00de771fcc430db4ae7f2cef7031022021-12-05T12:04:46ZEffects of adenovirus-mediated knockdown of IRAK4 on synovitis in the osteoarthritis rabbit model10.1186/s13075-021-02684-81478-6362https://doaj.org/article/ca00de771fcc430db4ae7f2cef7031022021-12-01T00:00:00Zhttps://doi.org/10.1186/s13075-021-02684-8https://doaj.org/toc/1478-6362Abstract Background The use of interleukin-1 receptor-associated kinase 4 (IRAK4) inhibitor as a treatment for the inflammatory joint disease is a promising method. However, its underlying mechanism in osteoarthritis (OA) remains unclear. The purpose of this study is to look into the effects of adenovirus-mediated knockdown of IRAK4 on synovitis in the OA rabbit model. Methods Ad-shIRAK4 was injected two weeks after anterior cruciate ligament resection. Six weeks later, the rabbits were killed. The expression of IRAK4, TNFR-associated factor 6(TRAF6), TGF-activated kinase 1(TAK1), p-IKB kinase (p-IKK), p-nuclear factor kappa-B (p-NFκB), p38, and p-p38 in the synovial membrane was detected by western blot, qRT-PCR, and immunohistochemistry analysis. Immunohistochemistry was to detect the expression of IRAK4 proteins in articular cartilage. H&E staining was to assess the pathological changes of synovium and cartilage. The levels of interleukin (IL)-1β, tumor necrosis factor-α(TNF-α), and MMP-13 in the synovial fluid were measured by ELISA. X-ray and micro-computerized tomography (μCT) scans were used to assess knee joint conditions and microstructure of subchondral bone. Results IRAK4 expression levels in synovial tissues of the OA model group exhibited a significant upward trend. Ad-shIRAK4 significantly reduced IRAK4 mRNA expression in synovium tissues. Notably, Ad-shIRAK4 suppressed the Toll-like receptor/interleukin-1 receptor (TLR/IL-1R) signaling. In addition, in the Ad-shIRAK4 treatment group, we can see less inflammatory cell infiltration and reduced hyperplasia and angiogenesis. The levels of IL-1β, TNF-α, and MMP-13 in the synovial fluid in the OA model group were significantly higher than that in the control group, which were reduced by Ad-shIRAK4 treatment. Finally, Results of HE stains, immunohistochemistry, and μCT showed that Ad-shIRAK4 treatment has a protective effect on cartilage damage. Conclusions IRAK4 is significantly upregulated in the synovium from the osteoarthritis rabbit model. In addition, Ad-shIRAK4 reduced the expression of IRAK4 and suppressed TLR/IL-1R signaling in the synovium from the osteoarthritis rabbit model. Ad-shIRAK4 could alleviate synovitis and cartilage degradation in the osteoarthritis rabbit model, and thus alleviate the symptoms of OA and prevent the progression of OA. Graphical abstractMuzhe LiHuiyun LiXun RanHan YinXuling LuoZhiwei ChenBMCarticleInterleukin-1 receptor-associated kinase 4SynovitisOsteoarthritisToll-like receptor/IL-1 receptorInflammationDiseases of the musculoskeletal systemRC925-935ENArthritis Research & Therapy, Vol 23, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Interleukin-1 receptor-associated kinase 4 Synovitis Osteoarthritis Toll-like receptor/IL-1 receptor Inflammation Diseases of the musculoskeletal system RC925-935
spellingShingle	Interleukin-1 receptor-associated kinase 4 Synovitis Osteoarthritis Toll-like receptor/IL-1 receptor Inflammation Diseases of the musculoskeletal system RC925-935 Muzhe Li Huiyun Li Xun Ran Han Yin Xuling Luo Zhiwei Chen Effects of adenovirus-mediated knockdown of IRAK4 on synovitis in the osteoarthritis rabbit model
description	Abstract Background The use of interleukin-1 receptor-associated kinase 4 (IRAK4) inhibitor as a treatment for the inflammatory joint disease is a promising method. However, its underlying mechanism in osteoarthritis (OA) remains unclear. The purpose of this study is to look into the effects of adenovirus-mediated knockdown of IRAK4 on synovitis in the OA rabbit model. Methods Ad-shIRAK4 was injected two weeks after anterior cruciate ligament resection. Six weeks later, the rabbits were killed. The expression of IRAK4, TNFR-associated factor 6(TRAF6), TGF-activated kinase 1(TAK1), p-IKB kinase (p-IKK), p-nuclear factor kappa-B (p-NFκB), p38, and p-p38 in the synovial membrane was detected by western blot, qRT-PCR, and immunohistochemistry analysis. Immunohistochemistry was to detect the expression of IRAK4 proteins in articular cartilage. H&E staining was to assess the pathological changes of synovium and cartilage. The levels of interleukin (IL)-1β, tumor necrosis factor-α(TNF-α), and MMP-13 in the synovial fluid were measured by ELISA. X-ray and micro-computerized tomography (μCT) scans were used to assess knee joint conditions and microstructure of subchondral bone. Results IRAK4 expression levels in synovial tissues of the OA model group exhibited a significant upward trend. Ad-shIRAK4 significantly reduced IRAK4 mRNA expression in synovium tissues. Notably, Ad-shIRAK4 suppressed the Toll-like receptor/interleukin-1 receptor (TLR/IL-1R) signaling. In addition, in the Ad-shIRAK4 treatment group, we can see less inflammatory cell infiltration and reduced hyperplasia and angiogenesis. The levels of IL-1β, TNF-α, and MMP-13 in the synovial fluid in the OA model group were significantly higher than that in the control group, which were reduced by Ad-shIRAK4 treatment. Finally, Results of HE stains, immunohistochemistry, and μCT showed that Ad-shIRAK4 treatment has a protective effect on cartilage damage. Conclusions IRAK4 is significantly upregulated in the synovium from the osteoarthritis rabbit model. In addition, Ad-shIRAK4 reduced the expression of IRAK4 and suppressed TLR/IL-1R signaling in the synovium from the osteoarthritis rabbit model. Ad-shIRAK4 could alleviate synovitis and cartilage degradation in the osteoarthritis rabbit model, and thus alleviate the symptoms of OA and prevent the progression of OA. Graphical abstract
format	article
author	Muzhe Li Huiyun Li Xun Ran Han Yin Xuling Luo Zhiwei Chen
author_facet	Muzhe Li Huiyun Li Xun Ran Han Yin Xuling Luo Zhiwei Chen
author_sort	Muzhe Li
title	Effects of adenovirus-mediated knockdown of IRAK4 on synovitis in the osteoarthritis rabbit model
title_short	Effects of adenovirus-mediated knockdown of IRAK4 on synovitis in the osteoarthritis rabbit model
title_full	Effects of adenovirus-mediated knockdown of IRAK4 on synovitis in the osteoarthritis rabbit model
title_fullStr	Effects of adenovirus-mediated knockdown of IRAK4 on synovitis in the osteoarthritis rabbit model
title_full_unstemmed	Effects of adenovirus-mediated knockdown of IRAK4 on synovitis in the osteoarthritis rabbit model
title_sort	effects of adenovirus-mediated knockdown of irak4 on synovitis in the osteoarthritis rabbit model
publisher	BMC
publishDate	2021
url	https://doaj.org/article/ca00de771fcc430db4ae7f2cef703102
work_keys_str_mv	AT muzheli effectsofadenovirusmediatedknockdownofirak4onsynovitisintheosteoarthritisrabbitmodel AT huiyunli effectsofadenovirusmediatedknockdownofirak4onsynovitisintheosteoarthritisrabbitmodel AT xunran effectsofadenovirusmediatedknockdownofirak4onsynovitisintheosteoarthritisrabbitmodel AT hanyin effectsofadenovirusmediatedknockdownofirak4onsynovitisintheosteoarthritisrabbitmodel AT xulingluo effectsofadenovirusmediatedknockdownofirak4onsynovitisintheosteoarthritisrabbitmodel AT zhiweichen effectsofadenovirusmediatedknockdownofirak4onsynovitisintheosteoarthritisrabbitmodel
_version_	1718372281347997696

Effects of adenovirus-mediated knockdown of IRAK4 on synovitis in the osteoarthritis rabbit model

Ejemplares similares