title: MicroRNA regulation associated chondrogenesis of mouse MSCs grown on polyhydroxyalkanoates.
abstract: Microbial polyhydroxyalkanoates (PHA) including poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) were found to induce chondrogenesis of mesenchymal stem cells (MSCs) and preserve chondrocytic phenotype as well as support chondrocytes-specific extracellular matrix (ECM) secretion. In this study, mouse MSCs cultured on the PHBHHx films for 24 h showed up-regulated expression of chondrogenic marker genes including aggrecan, col2, sox9, col10 and pthrp. To further illustrate this phenomonon, chondrogenesis-related microRNA expression profiling was examined by quantitative real-time PCR (RT-PCR) based on results of microRNA array obtained from comparison between mouse MSCs and mature mouse chondrocytes. Among 44 microRNAs related to chondrogenesis on microrray studies, considering only broadly-conserved microRNAs, seven differentially-expressed microRNAs were selected to study their target genes related to chondrogenesis. Two microRNAs out of the seven, namely, miR-29a and miR-29b, were revealed to directly target 3' UTR of col2a1 encoding type II collagen by dual-luciferase assay, and their activity was under the regulation of Sox9, the SRY-related high mobility group-box gene 9. For the first time microRNAs were shown to regulate the stem cell differentiation processes mediated by cell-material interactions.
authors.affiliation: Ministry of Education Key Laboratory of Bioinformatics, Department of Biological Sciences and Biotechnology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Yan
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Shen
authors.forename: Gang
authors.initials: G
authors.lastname: Yang
authors.forename: Jia
authors.initials: J
authors.lastname: Jian
authors.forename: Hua-Su
authors.initials: HS
authors.lastname: Wang
authors.forename: Guo-Qiang
authors.initials: GQ
authors.lastname: Chen
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wu
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020219:Chondrogenesis / Q000187:drug effects / Q000235:genetics*; D024043:Collagen Type II / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D054813:Polyhydroxyalkanoates / Q000494:pharmacology*; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055758:SOX9 Transcription Factor / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D015415:Biomarkers; C447413:Col2a1 protein, mouse; D024043:Collagen Type II; C547014:MIRN29 microRNA, mouse; D035683:MicroRNAs; D054813:Polyhydroxyalkanoates; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse