Two non-coding RNAs, MicroRNA-101 and HOTTIP contribute cartilage integrity by epigenetic and homeotic regulation of integrin-α1

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, HOITIP in the processes of endochondral ossification and osteoarthritic progression. In wing mesenchymal cells, up-expression of miR-101 by TGF-beta 3 treatment is targeting DNMT-3B and thereby altered the methylation of integrin-alpha 1 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-alpha 1, and resulted in cartilage destruction. In an OA animal model, introduction of lenti-viruses that encoded miR-101 or integrin-alpha 1 successfully reduced cartilage destruction. In like manner, long non-coding RNA (lncRNA), HOITIP, a known regulator for HoxA genes, was highly up-regulated and concurrent down-regulation of HoxA13 displayed the suppression of integrin-alpha 1 in OA chondrocytes. In conclusion, two non-coding RNAs, miR-101 and HOTTIP regulate cartilage development and destruction by modulating integrin-alpha 1 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. (C) 2013 Elsevier Inc. All rights reserved.