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

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2016 Apr 13

PMID 27070581

Citations 5

Authors

Dwaipayan Sen

Giridhara R Jayandharan

Affiliations

Soon will be listed here.

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.

Citing Articles

AAV mediated repression of Neat1 lncRNA combined with F8 gene augmentation mitigates pathological mediators of joint disease in haemophilia.

Sarangi P, Senthilkumar M, Amit S, Kumar N, Jayandharan G J Cell Mol Med. 2024; 28(11):e18460.

PMID: 38864710 PMC: 11167708. DOI: 10.1111/jcmm.18460.

Potential role of long non-coding RNA H19 and Neat1 in haemophilic arthropathy.

Sarangi P, Senthilkumar M, Kumar N, Senguttuvan S, Vasudevan M, Jayandharan G J Cell Mol Med. 2023; 27(12):1745-1749.

PMID: 37183540 PMC: 10273061. DOI: 10.1111/jcmm.17770.

The Possible Non-Mutational Causes of FVIII Deficiency: Non-Coding RNAs and Acquired Hemophilia A.

Zimta A, Hotea I, Brinza M, Blag C, Iluta S, Constantinescu C Front Med (Lausanne). 2021; 8:654197.

PMID: 33968959 PMC: 8099106. DOI: 10.3389/fmed.2021.654197.

The Progression of Hemophilic Arthropathy: The Role of Biomarkers.

Pasta G, Annunziata S, Polizzi A, Caliogna L, Jannelli E, Minen A Int J Mol Sci. 2020; 21(19).

PMID: 33023246 PMC: 7583947. DOI: 10.3390/ijms21197292.

Micromanaging aerobic respiration and glycolysis in cancer cells.

Orang A, Petersen J, McKinnon R, Michael M Mol Metab. 2019; 23:98-126.

PMID: 30837197 PMC: 6479761. DOI: 10.1016/j.molmet.2019.01.014.

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