{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T07:50:20Z","timestamp":1773388220210,"version":"3.50.1"},"reference-count":39,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2016,4,8]],"date-time":"2016-04-08T00:00:00Z","timestamp":1460073600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Science and Technology","award":["Swarnajayanti Fellowship 2011"],"award-info":[{"award-number":["Swarnajayanti Fellowship 2011"]}]},{"DOI":"10.13039\/501100010803","name":"Department of Biotechnology","doi-asserted-by":"publisher","award":["Senior Innovative Young Biotechnologist award 2010: BT\/03\/IYBA\/2010"],"award-info":[{"award-number":["Senior Innovative Young Biotechnologist award 2010: BT\/03\/IYBA\/2010"]}],"id":[{"id":"10.13039\/501100010803","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010803","name":"Department of Biotechnology","doi-asserted-by":"publisher","award":["BT\/PR5021\/MED\/30\/757\/2012"],"award-info":[{"award-number":["BT\/PR5021\/MED\/30\/757\/2012"]}],"id":[{"id":"10.13039\/501100010803","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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 \u03b1 (VEGF-\u03b1) and hypoxia inducing factor 2\u03b1 (HIF-2\u03b1), ~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.<\/jats:p>","DOI":"10.3390\/ijms17040492","type":"journal-article","created":{"date-parts":[[2016,4,8]],"date-time":"2016-04-08T21:02:38Z","timestamp":1460149358000},"page":"492","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["MicroRNA-15b Modulates Molecular Mediators of Blood Induced Arthropathy in Hemophilia Mice"],"prefix":"10.3390","volume":"17","author":[{"given":"Dwaipayan","family":"Sen","sequence":"first","affiliation":[{"name":"Department of Hematology, Christian Medical College, 632004 Vellore, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giridhara","family":"Jayandharan","sequence":"additional","affiliation":[{"name":"Department of Hematology, Christian Medical College, 632004 Vellore, India"},{"name":"Department of Biological Sciences and Bioengineering, Indian Institute of Technology, 208016 Kanpur, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2016,4,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1111\/j.1365-2516.2011.02669.x","article-title":"Exploring the biological basis of haemophilic joint disease: Experimental studies","volume":"18","author":"Valentino","year":"2012","journal-title":"Haemophilia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1002\/1529-0131(199905)42:5<1025::AID-ANR23>3.0.CO;2-3","article-title":"Blood-induced joint damage: A human in vitro study","volume":"42","author":"Roosendaal","year":"1999","journal-title":"Arthritis Rheum."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1302\/0301-620X.63B4.7298694","article-title":"The pathogenesis of chronic haemophilic arthropathy","volume":"63B","author":"Stein","year":"1981","journal-title":"J. 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