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http://dx.doi.org/10.14348/molcells.2014.0023

Upregulation of miR-23b Enhances the Autologous Therapeutic Potential for Degenerative Arthritis by Targeting PRKACB in Synovial Fluid-Derived Mesenchymal Stem Cells from Patients  

Ham, Onju (Cardiovascular Research Institute, Yonsei University College of Medicine)
Lee, Chang Youn (Department of Integrated Omics for Biomedical Sciences, Graduate School, Yonsei University)
Song, Byeong-Wook (Cardiovascular Research Institute, Yonsei University College of Medicine)
Lee, Se-Yeon (Cardiovascular Research Institute, Yonsei University College of Medicine)
Kim, Ran (Department of Biology Education, College of Education, Pusan National University)
Park, Jun-Hee (Department of Integrated Omics for Biomedical Sciences, Graduate School, Yonsei University)
Lee, Jiyun (Cardiovascular Research Institute, Yonsei University College of Medicine)
Seo, Hyang-Hee (Cardiovascular Research Institute, Yonsei University College of Medicine)
Lee, Chae Yoon (Department of Biology Education, College of Education, Pusan National University)
Chung, Yong-An (Institute of Catholic Integrative Medicine, Incheon St. Mary's Hospital, The Catholic University of Korea College of Medicine)
Maeng, Lee-So (Institute of Catholic Integrative Medicine, Incheon St. Mary's Hospital, The Catholic University of Korea College of Medicine)
Lee, Min Young (Department of Molecular Physiology, College of Pharmacy, Kyungpook National University)
Kim, Jongmin (Department of Life Systems, Sookmyung Women's University)
Hwang, Jihwan (Department of Microbiology, College of Natural Science, Pusan National University)
Woo, Dong Kyun (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University)
Chang, Woochul (Department of Biology Education, College of Education, Pusan National University)
Abstract
The use of synovial fluid-derived mesenchymal stem cells (SFMSCs) obtained from patients with degenerative arthropathy may serve as an alternative therapeutic strategy in osteoarthritis (OA) and rheumatoid arthritis (RA). For treatment of OA and RA patients, autologous transplantation of differentiated MSCs has several beneficial effects for cartilage regeneration including immunomodulatory activity. In this study, we induced chondrogenic differentiation of SFMSCs by inhibiting protein kinase A (PKA) with a small molecule and microRNA (miRNA). Chondrogenic differentiation was confirmed by PCR and immunocytochemistry using probes specific for aggrecan, the major cartilaginous proteoglycan gene. Absorbance of alcian blue stain to detect chondrogenic differentiation was increased in H-89 and/or miRNA-23b-transfected cells. Furthermore, expression of matrix metalloproteinase (MMP)-9 and MMP-2 was decreased in treated1 cells. Therefore, differentiation of SFMSCs into chondrocytes through inhibition of PKA signaling may be a therapeutic option for OA or RA patients.
Keywords
autologous cell transplantation; microRNAs; small molecules; synovial fluid-derived mesenchymal stem cells;
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