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Deferoxamine Suppresses Collagen Cleavage and Protease, Cytokine, and COL10A1 Expression and Upregulates AMPK and Krebs Cycle Genes in Human Osteoarthritic Cartilage
المؤلفون المشاركون
Antoniou, John
Zukor, David
Tchetina, Elena V.
Markova, Galina A.
Makarov, Sergey A.
Poole, A. Robin
Kuzin, Alexandr N.
المصدر
International Journal of Rheumatology
العدد
المجلد 2016، العدد 2016 (31 ديسمبر/كانون الأول 2016)، ص ص. 1-14، 14ص.
الناشر
Hindawi Publishing Corporation
تاريخ النشر
2016-11-30
دولة النشر
مصر
عدد الصفحات
14
التخصصات الرئيسية
الملخص EN
This study reports the effects of the iron chelator deferoxamine (DFO) on collagen cleavage, inflammation, and chondrocyte hypertrophy in relation to energy metabolism-related gene expression in osteoarthritic (OA) articular cartilage.
Full-depth explants of human OA knee articular cartilage from arthroplasty were cultured with exogenous DFO (1–50 μM).
Type II collagen cleavage and phospho-adenosine monophosphate-activated protein kinase (pAMPK) concentrations were measured using ELISAs.
Gene expression studies employed real-time PCR and included AMPK analyses in PBMCs.
In OA explants collagen cleavage was frequently downregulated by 10–50 μM DFO.
PCR analysis of 7 OA patient cartilages revealed that 10 μM DFO suppressed expression of MMP-1, MMP-13, IL-1β, and TNFα and a marker of chondrocyte hypertrophy, COL10A1.
No changes were observed in the expression of glycolysis-related genes.
In contrast, expressions of genes associated with the mitochondrial Krebs cycle (TCA), AMPK, HIF1α, and COL2A1 were upregulated.
AMPK gene expression was reduced in OA cartilage and increased in PBMCs from the same patients compared to healthy controls.
Our studies demonstrate that DFO is capable of suppressing excessive collagenase-mediated type II collagen cleavage in OA cartilage and reversing phenotypic changes.
The concomitant upregulation of proanabolic TCA-related gene expressions points to a potential for availability of energy generating substrates required for matrix repair by end-stage OA chondrocytes.
This might normally be prevented by high whole-body energy requirements indicated by elevated AMPK expression in PBMCs of OA patients.
نمط استشهاد جمعية علماء النفس الأمريكية (APA)
Tchetina, Elena V.& Markova, Galina A.& Poole, A. Robin& Zukor, David& Antoniou, John& Makarov, Sergey A.…[et al.]. 2016. Deferoxamine Suppresses Collagen Cleavage and Protease, Cytokine, and COL10A1 Expression and Upregulates AMPK and Krebs Cycle Genes in Human Osteoarthritic Cartilage. International Journal of Rheumatology،Vol. 2016, no. 2016, pp.1-14.
https://search.emarefa.net/detail/BIM-1106910
نمط استشهاد الجمعية الأمريكية للغات الحديثة (MLA)
Tchetina, Elena V.…[et al.]. Deferoxamine Suppresses Collagen Cleavage and Protease, Cytokine, and COL10A1 Expression and Upregulates AMPK and Krebs Cycle Genes in Human Osteoarthritic Cartilage. International Journal of Rheumatology No. 2016 (2016), pp.1-14.
https://search.emarefa.net/detail/BIM-1106910
نمط استشهاد الجمعية الطبية الأمريكية (AMA)
Tchetina, Elena V.& Markova, Galina A.& Poole, A. Robin& Zukor, David& Antoniou, John& Makarov, Sergey A.…[et al.]. Deferoxamine Suppresses Collagen Cleavage and Protease, Cytokine, and COL10A1 Expression and Upregulates AMPK and Krebs Cycle Genes in Human Osteoarthritic Cartilage. International Journal of Rheumatology. 2016. Vol. 2016, no. 2016, pp.1-14.
https://search.emarefa.net/detail/BIM-1106910
نوع البيانات
مقالات
لغة النص
الإنجليزية
الملاحظات
Includes bibliographical references
رقم السجل
BIM-1106910
قاعدة معامل التأثير والاستشهادات المرجعية العربي "ارسيف Arcif"
أضخم قاعدة بيانات عربية للاستشهادات المرجعية للمجلات العلمية المحكمة الصادرة في العالم العربي
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