title: The role of microRNA-23b in the differentiation of MSC into chondrocyte by targeting protein kinase A signaling.
abstract: Chondrogenic differentiation of mesenchymal stem cells (MSCs) is critical for successful cartilage regeneration. Several methods have been developed to attempt to chondrogenic differentiation, because chondrogenic differentiated cells can form stable cartilage and induce expression of a cartilage-specific phenotype. In this study, we found that both H-89 and microRNA-23b induced differentiation into chondrocyte of hMSCs through down-regulation of protein kinase A (PKA) signaling. The small molecule, H-89, was identified by PCA analysis as a potential mediator of chondrogenic differentiation. H-89 induced the expression of the chondrocyte marker, aggrecan, as well as miR-23b. We searched that miR-23b regulates protein level of PKA. When miR-23b was transfected into hMSCs, chondrogenic differentiation was induced. We confirmed the target of miR-23b using a reporter gene assay. Furthermore, not only H-89 or miR-23b-treated cells, but also cell co-treated with H-89 and miR-23b differentiated into chondrocytes. Our results indicate that H-89 induces the expression of endogenous miR-23b, thereby inducing chondrogenic differentiation by negatively inhibition of PKA signaling.
authors.affiliation: Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Onju
authors.initials: O
authors.lastname: Ham
authors.forename: Byeong-Wook
authors.initials: BW
authors.lastname: Song
authors.forename: Se-Yeon
authors.initials: SY
authors.lastname: Lee
authors.forename: Eunmi
authors.initials: E
authors.lastname: Choi
authors.forename: Min-Ji
authors.initials: MJ
authors.lastname: Cha
authors.forename: Chang Youn
authors.initials: CY
authors.lastname: Lee
authors.forename: Jun-Hee
authors.initials: JH
authors.lastname: Park
authors.forename: Il-Kwon
authors.initials: IK
authors.lastname: Kim
authors.forename: Woochul
authors.initials: W
authors.lastname: Chang
authors.forename: Soyeon
authors.initials: S
authors.lastname: Lim
authors.forename: Chang Hyun
authors.initials: CH
authors.lastname: Lee
authors.forename: Soonhag
authors.initials: S
authors.lastname: Kim
authors.forename: Yangsoo
authors.initials: Y
authors.lastname: Jang
authors.forename: Ki-Chul
authors.initials: KC
authors.lastname: Hwang
mesh_terms: D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology* / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007546:Isoquinolines / Q000494:pharmacology; D035683:MicroRNAs / Q000235:genetics* / Q000502:physiology; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D007546:Isoquinolines; C552430:MIRN23a microRNA, human; D035683:MicroRNAs; D013449:Sulfonamides; D017868:Cyclic AMP-Dependent Protein Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide