دورية أكاديمية
CCN3 (NOV) Drives Degradative Changes in Aging Articular Cartilage
| العنوان: | CCN3 (NOV) Drives Degradative Changes in Aging Articular Cartilage |
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| المؤلفون: | Miho Kuwahara, Koichi Kadoya, Sei Kondo, Shanqi Fu, Yoshiko Miyake, Ayako Ogo, Mitsuaki Ono, Takayuki Furumatsu, Eiji Nakata, Takako Sasaki, Shogo Minagi, Masaharu Takigawa, Satoshi Kubota, Takako Hattori |
| المصدر: | International Journal of Molecular Sciences, Vol 21, Iss 20, p 7556 (2020) |
| بيانات النشر: | MDPI AG, 2020. |
| سنة النشر: | 2020 |
| المجموعة: | LCC:Biology (General) LCC:Chemistry |
| مصطلحات موضوعية: | cellular communication network factor 3, CCN3, NOV, primary chondrocytes, aging, oxidative stress, Biology (General), QH301-705.5, Chemistry, QD1-999 |
| الوصف: | Aging is a major risk factor of osteoarthritis, which is characterized by the degeneration of articular cartilage. CCN3, a member of the CCN family, is expressed in cartilage and has various physiological functions during chondrocyte development, differentiation, and regeneration. Here, we examine the role of CCN3 in cartilage maintenance. During aging, the expression of Ccn3 mRNA in mouse primary chondrocytes from knee cartilage increased and showed a positive correlation with p21 and p53 mRNA. Increased accumulation of CCN3 protein was confirmed. To analyze the effects of CCN3 in vitro, either primary cultured human articular chondrocytes or rat chondrosarcoma cell line (RCS) were used. Artificial senescence induced by H2O2 caused a dose-dependent increase in Ccn3 gene and CCN3 protein expression, along with enhanced expression of p21 and p53 mRNA and proteins, as well as SA-β gal activity. Overexpression of CCN3 also enhanced p21 promoter activity via p53. Accordingly, the addition of recombinant CCN3 protein to the culture increased the expression of p21 and p53 mRNAs. We have produced cartilage-specific CCN3-overexpressing transgenic mice, and found degradative changes in knee joints within two months. Inflammatory gene expression was found even in the rib chondrocytes of three-month-old transgenic mice. Similar results were observed in human knee articular chondrocytes from patients at both mRNA and protein levels. These results indicate that CCN3 is a new senescence marker of chondrocytes, and the overexpression of CCN3 in cartilage may in part promote chondrocyte senescence, leading to the degeneration of articular cartilage through the induction of p53 and p21. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1422-0067 1661-6596 |
| Relation: | https://www.mdpi.com/1422-0067/21/20/7556; https://doaj.org/toc/1661-6596; https://doaj.org/toc/1422-0067 |
| DOI: | 10.3390/ijms21207556 |
| URL الوصول: | https://doaj.org/article/88701c5c22f9436b8f6147e814c8deb5 |
| رقم الأكسشن: | edsdoj.88701c5c22f9436b8f6147e814c8deb5 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 14220067 16616596 |
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| DOI: | 10.3390/ijms21207556 |