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Int. J. Mol. Sci. 2016, 17(4), 492;

MicroRNA-15b Modulates Molecular Mediators of Blood Induced Arthropathy in Hemophilia Mice

Department of Hematology, Christian Medical College, 632004 Vellore, India
Department of Biological Sciences and Bioengineering, Indian Institute of Technology, 208016 Kanpur, India
Author to whom correspondence should be addressed.
Academic Editor: William Chi-shing Cho
Received: 24 January 2016 / Revised: 21 March 2016 / Accepted: 25 March 2016 / Published: 8 April 2016
(This article belongs to the Special Issue MicroRNA in Various Disease States as Biomarkers)
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The development of arthropathy is a major co-morbidity in patients with hemophilia. The present study was designed to study the role of a microRNA biomarker (miR-15b) in the development of joint disease. To investigate the expression profile of miR-15b during the development of arthropathy, we first isolated and studied small RNA from the acute and chronic hemarthrosis model of hemophilia A mice. We observed that miR-15b was consistently repressed (~1- to 4-fold) from the onset of joint bleeding (1, 3, 7 and 24 h) until six bleeding episodes (up to 90 days). To test if reconstitution of miR-15b modulates biomarkers of joint damage in a chronic hemarthrosis model, we administered an adeno-associated virus (AAV) 5-miR-15b vector intra-articularly alone or in combination with systemic administration of AAV2-factor VIII. miR-15b overexpression downregulated markers of angiogenesis and hypoxia (vascular epithelial growth factor α (VEGF-α) and hypoxia inducing factor 2α (HIF-2α), ~70% and ~34%, respectively) in the affected joints. In addition, the co-administration of miR-15b and factor VIII vectors reduced the levels of the chondrodegenerative matrix-metalloproteinases (MMPs) 1, 3, 9 and 14 (~14% to 60%) in the injured joints. These data demonstrate for the first time the role of a miR-15b in the development of hemophilic arthropathy and has implications in development of miR based therapies for joint disease. View Full-Text
Keywords: microRNA; factor VIII; hemophilia A; murine model microRNA; factor VIII; hemophilia A; murine model

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Sen, D.; Jayandharan, G.R. MicroRNA-15b Modulates Molecular Mediators of Blood Induced Arthropathy in Hemophilia Mice. Int. J. Mol. Sci. 2016, 17, 492.

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