دورية أكاديمية
Dickkopf-3 (DKK3) Signaling in IL-1a-Challenged Chondrocytes: Involvement of the NF-?B Pathway
| العنوان: | Dickkopf-3 (DKK3) Signaling in IL-1a-Challenged Chondrocytes: Involvement of the NF-?B Pathway |
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| المؤلفون: | Conde, Javier, Ruiz-Fernandez, Clara, Francisco, Vera, Scotece, Morena, Gómez, Rodolfo, Lago, Francisca, González-Gay Mantecón, Miguel Ángel, Pino, Jesús, Mobasheri, Ali, Gualillo, Oreste |
| المساهمون: | Universidad de Cantabria |
| المصدر: | Cartilage . 2021 Dec;13(2_suppl):925S-934S |
| بيانات النشر: | SAGE Publications Ltd |
| سنة النشر: | 2021 |
| المجموعة: | Universidad de Cantabria: UCrea |
| مصطلحات موضوعية: | Chondrocyte, Inflammation, Metalloprotease |
| الوصف: | Objective: Osteoarthritis (OA) is an age-related biomechanical and low-grade inflammometabolic disease of the joints and one of the costliest and disabling forms of arthritis. Studies on matrix-degrading enzymes such as metalloproteases, which are implicated in the increased catabolism of extracellular matrix, are of paramount relevance. DKK3 is a member of DKK family and is best known for its role in cancer. Although there is some information about the participation of DKK3 in cartilage pathophysiology and on metalloproteases regulation, in particular, little is known about DKK3 signaling mechanisms. Thus, the aim of this study is to explore how DKK3 regulates matrix metalloproteinase-13 (MMP-13) expression. Design: Gene, protein expression and protein phosphorylation in primary human chondrocytes and ATDC5 mouse cells were assessed by RT-qPCR and Western blot analysis. Further studies on DKK3 activity were performed by targeting DKK3 gene with a specific siRNA. Results: DKK3 expression was found to be higher in OA human chondrocytes than healthy cells, being its expression decreased in interleukin-1? (IL-1?)-stimulated cells. DKK3 knockdown increased the induction of MMP-13 elicited by IL-1? in human and mouse chondrocytes and after the analysis of different signalling pathways, we observed that NF-?B pathway was involved in the regulation of MMP-13 expression by DKK3. Conclusions: Herein we have demonstrated, for the first time, that DKK3 gene silencing exacerbated NF-?B activation, resulting in an increased IL-1?-driven induction of MMP-13. Our results further confirm that DKK3 may play a protective role in OA by attenuating NF-?B activation and the subsequent production of metalloproteases. ; Funding: OG and FL are Staff Personnel of Xunta de Galicia (Servizo Galego de Saude, SERGAS) through a research-staff stabilization contract (ISCIII/SERGAS). JC is “Miguel Servet” Researcher “CP19/00172 (ISCIII/FEDER), MS and VF are currently “Sara Borrell” Researchers funded by ISCIII and FEDER (CD16/00111). RG is a ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1947-6035 1947-6043 |
| العلاقة: | https://doi.org/10.1177/1947603520933328Test; http://hdl.handle.net/10902/24455Test |
| DOI: | 10.1177/1947603520933328 |
| الإتاحة: | https://doi.org/10.1177/1947603520933328Test http://hdl.handle.net/10902/24455Test |
| حقوق: | © The Author(s) 2020. Reprinted by permission of SAGE Publications. ; openAccess |
| رقم الانضمام: | edsbas.E98AB840 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 19476035 19476043 |
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| DOI: | 10.1177/1947603520933328 |