Susceptibility of cyclin-dependent kinase inhibitor 1-deficient mice to rheumatoid arthritis arising from interleukin-1β-induced inflammation

Abstract We recently reported that cyclin-dependent kinase inhibitor 1 (p21) deficiency induces osteoarthritis susceptibility. Here, we determined the mechanism underlying the effect of p21 in synovial and cartilage tissues in RA. The knee joints of p21-knockout (p21−/−) (n = 16) and wild type C57BL...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Yoshinori Takashima, Shinya Hayashi, Koji Fukuda, Toshihisa Maeda, Masanori Tsubosaka, Tomoyuki Kamenaga, Kenichi Kikuchi, Masahiro Fujita, Yuichi Kuroda, Shingo Hashimoto, Naoki Nakano, Tomoyuki Matsumoto, Ryosuke Kuroda
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e0390f33230240bcb695e5747694aa75
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:e0390f33230240bcb695e5747694aa75
record_format	dspace
spelling	oai:doaj.org-article:e0390f33230240bcb695e5747694aa752021-12-02T16:04:22ZSusceptibility of cyclin-dependent kinase inhibitor 1-deficient mice to rheumatoid arthritis arising from interleukin-1β-induced inflammation10.1038/s41598-021-92055-92045-2322https://doaj.org/article/e0390f33230240bcb695e5747694aa752021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92055-9https://doaj.org/toc/2045-2322Abstract We recently reported that cyclin-dependent kinase inhibitor 1 (p21) deficiency induces osteoarthritis susceptibility. Here, we determined the mechanism underlying the effect of p21 in synovial and cartilage tissues in RA. The knee joints of p21-knockout (p21−/−) (n = 16) and wild type C57BL/6 (p21+/+) mice (n = 16) served as in vivo models of collagen antibody-induced arthritis (CAIA). Arthritis severity was evaluated by immunological and histological analyses. The response of p21 small-interfering RNA (siRNA)-treated human RA FLSs (n = 5 per group) to interleukin (IL)-1β stimulation was determined in vitro. Arthritis scores were higher in p21−/− mice than in p21+/+ mice. More severe synovitis, earlier loss of Safranin-O staining, and cartilage destruction were observed in p21−/− mice compared to p21+/+ mice. p21−/− mice expressed higher levels of IL-1β, TNF-α, F4/80, CD86, p-IKKα/β, and matrix metalloproteinases (MMPs) in cartilage and synovial tissues via IL-1β-induced NF-kB signaling. IL-1β stimulation significantly increased IL-6, IL-8, and MMP expression, and enhanced IKKα/β and IκBα phosphorylation in human FLSs. p21-deficient CAIA mice are susceptible to RA phenotype alterations, including joint cartilage destruction and severe synovitis. Therefore, p21 may have a regulatory role in inflammatory cytokine production including IL-1β, IL-6, and TNF-α.Yoshinori TakashimaShinya HayashiKoji FukudaToshihisa MaedaMasanori TsubosakaTomoyuki KamenagaKenichi KikuchiMasahiro FujitaYuichi KurodaShingo HashimotoNaoki NakanoTomoyuki MatsumotoRyosuke KurodaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yoshinori Takashima Shinya Hayashi Koji Fukuda Toshihisa Maeda Masanori Tsubosaka Tomoyuki Kamenaga Kenichi Kikuchi Masahiro Fujita Yuichi Kuroda Shingo Hashimoto Naoki Nakano Tomoyuki Matsumoto Ryosuke Kuroda Susceptibility of cyclin-dependent kinase inhibitor 1-deficient mice to rheumatoid arthritis arising from interleukin-1β-induced inflammation
description	Abstract We recently reported that cyclin-dependent kinase inhibitor 1 (p21) deficiency induces osteoarthritis susceptibility. Here, we determined the mechanism underlying the effect of p21 in synovial and cartilage tissues in RA. The knee joints of p21-knockout (p21−/−) (n = 16) and wild type C57BL/6 (p21+/+) mice (n = 16) served as in vivo models of collagen antibody-induced arthritis (CAIA). Arthritis severity was evaluated by immunological and histological analyses. The response of p21 small-interfering RNA (siRNA)-treated human RA FLSs (n = 5 per group) to interleukin (IL)-1β stimulation was determined in vitro. Arthritis scores were higher in p21−/− mice than in p21+/+ mice. More severe synovitis, earlier loss of Safranin-O staining, and cartilage destruction were observed in p21−/− mice compared to p21+/+ mice. p21−/− mice expressed higher levels of IL-1β, TNF-α, F4/80, CD86, p-IKKα/β, and matrix metalloproteinases (MMPs) in cartilage and synovial tissues via IL-1β-induced NF-kB signaling. IL-1β stimulation significantly increased IL-6, IL-8, and MMP expression, and enhanced IKKα/β and IκBα phosphorylation in human FLSs. p21-deficient CAIA mice are susceptible to RA phenotype alterations, including joint cartilage destruction and severe synovitis. Therefore, p21 may have a regulatory role in inflammatory cytokine production including IL-1β, IL-6, and TNF-α.
format	article
author	Yoshinori Takashima Shinya Hayashi Koji Fukuda Toshihisa Maeda Masanori Tsubosaka Tomoyuki Kamenaga Kenichi Kikuchi Masahiro Fujita Yuichi Kuroda Shingo Hashimoto Naoki Nakano Tomoyuki Matsumoto Ryosuke Kuroda
author_facet	Yoshinori Takashima Shinya Hayashi Koji Fukuda Toshihisa Maeda Masanori Tsubosaka Tomoyuki Kamenaga Kenichi Kikuchi Masahiro Fujita Yuichi Kuroda Shingo Hashimoto Naoki Nakano Tomoyuki Matsumoto Ryosuke Kuroda
author_sort	Yoshinori Takashima
title	Susceptibility of cyclin-dependent kinase inhibitor 1-deficient mice to rheumatoid arthritis arising from interleukin-1β-induced inflammation
title_short	Susceptibility of cyclin-dependent kinase inhibitor 1-deficient mice to rheumatoid arthritis arising from interleukin-1β-induced inflammation
title_full	Susceptibility of cyclin-dependent kinase inhibitor 1-deficient mice to rheumatoid arthritis arising from interleukin-1β-induced inflammation
title_fullStr	Susceptibility of cyclin-dependent kinase inhibitor 1-deficient mice to rheumatoid arthritis arising from interleukin-1β-induced inflammation
title_full_unstemmed	Susceptibility of cyclin-dependent kinase inhibitor 1-deficient mice to rheumatoid arthritis arising from interleukin-1β-induced inflammation
title_sort	susceptibility of cyclin-dependent kinase inhibitor 1-deficient mice to rheumatoid arthritis arising from interleukin-1β-induced inflammation
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/e0390f33230240bcb695e5747694aa75
work_keys_str_mv	AT yoshinoritakashima susceptibilityofcyclindependentkinaseinhibitor1deficientmicetorheumatoidarthritisarisingfrominterleukin1binducedinflammation AT shinyahayashi susceptibilityofcyclindependentkinaseinhibitor1deficientmicetorheumatoidarthritisarisingfrominterleukin1binducedinflammation AT kojifukuda susceptibilityofcyclindependentkinaseinhibitor1deficientmicetorheumatoidarthritisarisingfrominterleukin1binducedinflammation AT toshihisamaeda susceptibilityofcyclindependentkinaseinhibitor1deficientmicetorheumatoidarthritisarisingfrominterleukin1binducedinflammation AT masanoritsubosaka susceptibilityofcyclindependentkinaseinhibitor1deficientmicetorheumatoidarthritisarisingfrominterleukin1binducedinflammation AT tomoyukikamenaga susceptibilityofcyclindependentkinaseinhibitor1deficientmicetorheumatoidarthritisarisingfrominterleukin1binducedinflammation AT kenichikikuchi susceptibilityofcyclindependentkinaseinhibitor1deficientmicetorheumatoidarthritisarisingfrominterleukin1binducedinflammation AT masahirofujita susceptibilityofcyclindependentkinaseinhibitor1deficientmicetorheumatoidarthritisarisingfrominterleukin1binducedinflammation AT yuichikuroda susceptibilityofcyclindependentkinaseinhibitor1deficientmicetorheumatoidarthritisarisingfrominterleukin1binducedinflammation AT shingohashimoto susceptibilityofcyclindependentkinaseinhibitor1deficientmicetorheumatoidarthritisarisingfrominterleukin1binducedinflammation AT naokinakano susceptibilityofcyclindependentkinaseinhibitor1deficientmicetorheumatoidarthritisarisingfrominterleukin1binducedinflammation AT tomoyukimatsumoto susceptibilityofcyclindependentkinaseinhibitor1deficientmicetorheumatoidarthritisarisingfrominterleukin1binducedinflammation AT ryosukekuroda susceptibilityofcyclindependentkinaseinhibitor1deficientmicetorheumatoidarthritisarisingfrominterleukin1binducedinflammation
_version_	1718385239333535744

Susceptibility of cyclin-dependent kinase inhibitor 1-deficient mice to rheumatoid arthritis arising from interleukin-1β-induced inflammation

Ejemplares similares