دورية أكاديمية
Susceptibility of cyclin-dependent kinase inhibitor 1-deficient mice to rheumatoid arthritis arising from interleukin-1β-induced inflammation
| العنوان: | Susceptibility of cyclin-dependent kinase inhibitor 1-deficient mice to rheumatoid arthritis arising from interleukin-1β-induced inflammation |
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| المؤلفون: | 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 |
| المصدر: | Scientific Reports, Vol 11, Iss 1, Pp 1-15 (2021) |
| بيانات النشر: | Nature Portfolio, 2021. |
| سنة النشر: | 2021 |
| المجموعة: | LCC:Medicine LCC:Science |
| مصطلحات موضوعية: | Medicine, Science |
| الوصف: | 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. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2045-2322 |
| العلاقة: | https://doaj.org/toc/2045-2322Test |
| DOI: | 10.1038/s41598-021-92055-9 |
| الوصول الحر: | https://doaj.org/article/e0390f33230240bcb695e5747694aa75Test |
| رقم الانضمام: | edsdoj.0390f33230240bcb695e5747694aa75 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 20452322 |
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| DOI: | 10.1038/s41598-021-92055-9 |