title: Upregulation of miR-23b enhances the autologous therapeutic potential for degenerative arthritis by targeting PRKACB in synovial fluid-derived mesenchymal stem cells from patients.
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-23btransfected cells. Furthermore, expression of matrix metalloproteinase (MMP)-9 and MMP-2 was decreased in treated cells. Therefore, differentiation of SFMSCs into chondrocytes through inhibition of PKA signaling may be a therapeutic option for OA or RA patients.
authors.affiliation: Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul 120-752, Korea ; Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Korea.
authors.forename: Onju
authors.initials: O
authors.lastname: Ham
authors.forename: Chang Youn
authors.initials: CY
authors.lastname: Lee
authors.forename: Byeong-Wook
authors.initials: BW
authors.lastname: Song
authors.forename: Se-Yeon
authors.initials: SY
authors.lastname: Lee
authors.forename: Ran
authors.initials: R
authors.lastname: Kim
authors.forename: Jun-Hee
authors.initials: JH
authors.lastname: Park
authors.forename: Jiyun
authors.initials: J
authors.lastname: Lee
authors.forename: Hyang-Hee
authors.initials: HH
authors.lastname: Seo
authors.forename: Chae Yoon
authors.initials: CY
authors.lastname: Lee
authors.forename: Yong-An
authors.initials: YA
authors.lastname: Chung
authors.forename: Lee-So
authors.initials: LS
authors.lastname: Maeng
authors.forename: Min Young
authors.initials: MY
authors.lastname: Lee
authors.forename: Jongmin
authors.initials: J
authors.lastname: Kim
authors.forename: Jihwan
authors.initials: J
authors.lastname: Hwang
authors.forename: Dong Kyun
authors.initials: DK
authors.lastname: Woo
authors.forename: Woochul
authors.initials: W
authors.lastname: Chang
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism; D017364:Collagenases / Q000378:metabolism; D054751:Cyclic AMP-Dependent Protein Kinase Catalytic Subunits / Q000037:antagonists & inhibitors*; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D035683:MicroRNAs / Q000235:genetics*; D010003:Osteoarthritis / Q000235:genetics / Q000628:therapy*; D013449:Sulfonamides / Q000494:pharmacology*; D013582:Synovial Fluid / Q000166:cytology*
chemical_list: D007546:Isoquinolines; C552430:MIRN23a microRNA, human; D035683:MicroRNAs; D013449:Sulfonamides; D054751:Cyclic AMP-Dependent Protein Kinase Catalytic Subunits; C517760:PRKACB protein, human; D017364:Collagenases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide