title: Two non-coding RNAs, MicroRNA-101 and HOTTIP contribute cartilage integrity by epigenetic and homeotic regulation of integrin-α1.
abstract: Non-coding RNAs have been less studied in cartilage development and destruction regulated by sophisticated molecular events despite their considerable theranostic potential. In this study, we identified significant down-regulation of mR-101 and up-regulation of lncRNA, HOTTIP in the processes of endochondral ossification and osteoarthritic progression. In wing mesenchymal cells, up-expression of miR-101 by TGF-β3 treatment is targeting DNMT-3B and thereby altered the methylation of integrin-α1 addressed as a positive regulator of endochondral ossification in this study. In like manner, down-regulation of miR-101 also coordinately up-regulated DNMT-3B, down-regulated integrin-α1, and resulted in cartilage destruction. In an OA animal model, introduction of lentiviruses that encoded miR-101 or integrin-α1 successfully reduced cartilage destruction. In like manner, long non-coding RNA (lncRNA), HOTTIP, a known regulator for HoxA genes, was highly up-regulated and concurrent down-regulation of HoxA13 displayed the suppression of integrin-α1 in OA chondrocytes. In conclusion, two non-coding RNAs, miR-101 and HOTTIP regulate cartilage development and destruction by modulating integrin-α1 either epigenetically by DNMT-3B or transcriptionally by HoxA13 and data further suggest that these non-coding RNAs could be a potent predictive biomarker for OA as well as a therapeutic target for preventing cartilage-related diseases.
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Wonkwang University, Iksan, Chunbuk 570-749, Republic of Korea.
authors.forename: Dongkyun
authors.initials: D
authors.lastname: Kim
authors.forename: Jinsoo
authors.initials: J
authors.lastname: Song
authors.forename: Jiyeon
authors.initials: J
authors.lastname: Han
authors.forename: Yunha
authors.initials: Y
authors.lastname: Kim
authors.forename: Churl-Hong
authors.initials: CH
authors.lastname: Chun
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Jin
mesh_terms: D000818:Animals; D002356:Cartilage / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D002645:Chickens; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D039423:Integrin alpha1 / Q000235:genetics*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D010003:Osteoarthritis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016372:RNA, Antisense / Q000235:genetics / Q000378:metabolism*; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D000097584:DNA Methyltransferase 3B
chemical_list: D004248:DNA (Cytosine-5-)-Methyltransferases; D018398:Homeodomain Proteins; D039423:Integrin alpha1; D035683:MicroRNAs; D016372:RNA, Antisense; D062085:RNA, Long Noncoding; D016212:Transforming Growth Factor beta; D000097584:DNA Methyltransferase 3B; C534072:MIRN101 microRNA, human; C099959:homeobox protein HOXA13
keywords: DNMT-3B; Endochondral ossification; HOTTIP; Integrin α1; MiR-101; Osteoarthritis