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Inhibition of miR-449a Promotes Cartilage Regeneration and Prevents Progression of Osteoarthritis in In Vivo Rat Models.

Authors
 Dawoon Baek  ;  Kyoung-Mi Lee  ;  Ki Won Park  ;  Jae Wan Suh  ;  Seong Mi Choi  ;  Kwang Hwan Park  ;  Jin Woo Lee  ;  Sung-Hwan Kim 
Citation
 Molecular Therapy. Nucleic Acids, Vol.13 : 322-333, 2018 
Journal Title
 Molecular Therapy. Nucleic Acids 
Issue Date
2018
Keywords
cartilage regeneration ; human mesenchymal stem cell ; miR-449a ; microRNA ; osteoarthritis
Abstract
Traumatic and degenerative lesions of articular cartilage usually progress to osteoarthritis (OA), a leading cause of disability in humans. MicroRNAs (miRNAs) can regulate the differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs) and play important roles in the expression of genes related to OA. However, their functional roles in OA remain poorly understood. Here, we have examined miR-449a, which targets sirtuin 1 (SIRT1) and lymphoid enhancer-binding factor-1 (LEF-1), and observed its effects on damaged cartilage. The levels of chondrogenic markers and miR-449a target genes increased during chondrogenesis in anti-miR-449a-transfected hBMSCs. A locked nucleic acid (LNA)-anti-miR-449a increased cartilage regeneration and expression of type II collagen and aggrecan on the regenerated cartilage surface in acute defect and OA models. Furthermore, intra-articular injection of LNA-anti-miR-449a prevented disease progression in the OA model. Our study indicates that miR-449a may be a novel potential therapeutic target for age-related joint diseases like OA.
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/165287
Files in This Item:
T201803773.pdf Download
DOI
10.1016/j.omtn.2018.09.015
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Orthopedic Surgery (정형외과학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부)
Yonsei Authors
김성환(Kim, Sung Hwan) ORCID logo https://orcid.org/0000-0001-5743-6241
박광환(Park, Kwang Hwan)
백다운(Baek, Dawoon) ORCID logo https://orcid.org/0000-0002-3794-6153
이경미(Lee, Kyoung Mi) ORCID logo https://orcid.org/0000-0002-9038-8162
이진우(Lee, Jin Woo)
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