Inhibition of miR-449a Promotes Cartilage Regeneration and Prevents Progression of Osteoarthritis in In Vivo Rat Models
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 g...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2018-12-01
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| Series: | Molecular Therapy: Nucleic Acids |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253118302592 |
| _version_ | 1829116928534249472 |
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| author | Dawoon Baek Kyoung-Mi Lee Ki Won Park Jae Wan Suh Seong Mi Choi Kwang Hwan Park Jin Woo Lee Sung-Hwan Kim |
| author_facet | Dawoon Baek Kyoung-Mi Lee Ki Won Park Jae Wan Suh Seong Mi Choi Kwang Hwan Park Jin Woo Lee Sung-Hwan Kim |
| author_sort | Dawoon Baek |
| collection | DOAJ |
| description | 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. Keywords: human mesenchymal stem cell, osteoarthritis, microRNA, miR-449a, cartilage regeneration |
| first_indexed | 2024-12-12T20:20:02Z |
| format | Article |
| id | doaj.art-0d07c238113647aea6c29f876a2db93f |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-12-12T20:20:02Z |
| publishDate | 2018-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-0d07c238113647aea6c29f876a2db93f2022-12-22T00:13:17ZengElsevierMolecular Therapy: Nucleic Acids2162-25312018-12-0113322333Inhibition of miR-449a Promotes Cartilage Regeneration and Prevents Progression of Osteoarthritis in In Vivo Rat ModelsDawoon Baek0Kyoung-Mi Lee1Ki Won Park2Jae Wan Suh3Seong Mi Choi4Kwang Hwan Park5Jin Woo Lee6Sung-Hwan Kim7Department of Orthopaedic Surgery, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, South Korea; Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, South KoreaDepartment of Orthopaedic Surgery, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, South Korea; Severance Biomedical Science Institute, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, South KoreaDepartment of Orthopaedic Surgery, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, South Korea; Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, South KoreaDepartment of Orthopaedic Surgery, Dankook University Hospital, Dankook University College of Medicine, 201 Manghyang-ro, Dongnam-gu, Cheonan 31116, South KoreaDepartment of Orthopaedic Surgery, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, South Korea; Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, South KoreaDepartment of Orthopaedic Surgery, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, South KoreaDepartment of Orthopaedic Surgery, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, South Korea; Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, South Korea; Severance Biomedical Science Institute, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, South Korea; Corresponding author: Jin Woo Lee, Department of Orthopaedic Surgery, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, South Korea.Department of Orthopaedic Surgery, Yonsei University College of Medicine, Gangnam Severance Hospital, 211 Eonju-ro, Gangnam-gu, Seoul 06273, South Korea; Corresponding author: Sung-Hwan Kim, Department of Orthopaedic Surgery, Yonsei University College of Medicine, Gangnam Severance Hospital, 211 Eonju-ro, Gangnam-gu, Seoul 06273, South Korea.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. Keywords: human mesenchymal stem cell, osteoarthritis, microRNA, miR-449a, cartilage regenerationhttp://www.sciencedirect.com/science/article/pii/S2162253118302592 |
| spellingShingle | Dawoon Baek Kyoung-Mi Lee Ki Won Park Jae Wan Suh Seong Mi Choi Kwang Hwan Park Jin Woo Lee Sung-Hwan Kim Inhibition of miR-449a Promotes Cartilage Regeneration and Prevents Progression of Osteoarthritis in In Vivo Rat Models Molecular Therapy: Nucleic Acids |
| title | Inhibition of miR-449a Promotes Cartilage Regeneration and Prevents Progression of Osteoarthritis in In Vivo Rat Models |
| title_full | Inhibition of miR-449a Promotes Cartilage Regeneration and Prevents Progression of Osteoarthritis in In Vivo Rat Models |
| title_fullStr | Inhibition of miR-449a Promotes Cartilage Regeneration and Prevents Progression of Osteoarthritis in In Vivo Rat Models |
| title_full_unstemmed | Inhibition of miR-449a Promotes Cartilage Regeneration and Prevents Progression of Osteoarthritis in In Vivo Rat Models |
| title_short | Inhibition of miR-449a Promotes Cartilage Regeneration and Prevents Progression of Osteoarthritis in In Vivo Rat Models |
| title_sort | inhibition of mir 449a promotes cartilage regeneration and prevents progression of osteoarthritis in in vivo rat models |
| url | http://www.sciencedirect.com/science/article/pii/S2162253118302592 |
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