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Int. J. Mol. Sci. 2016, 17(4), 492; doi:10.3390/ijms17040492

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

1
Department of Hematology, Christian Medical College, 632004 Vellore, India
2
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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Abstract

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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