PMID- 31284128 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200930 IS - 2162-2531 (Print) IS - 2162-2531 (Electronic) IS - 2162-2531 (Linking) VI - 17 DP - 2019 Sep 6 TI - miR-892b Inhibits Hypertrophy by Targeting KLF10 in the Chondrogenesis of Mesenchymal Stem Cells. PG - 310-322 LID - S2162-2531(19)30162-3 [pii] LID - 10.1016/j.omtn.2019.05.029 [doi] AB - We investigated the functional role of miR-892b as a novel inhibitor of chondrocyte hypertrophy during TGF-beta-mediated chondrogenesis of human mesenchymal stem cells (hMSCs). The expression of miR-892b during TGF-beta-mediated chondrogenesis of hMSCs and the effects of miR-892b overexpression on chondrogenic and hypertrophic marker genes in the chondrogenesis of hMSCs were investigated. Targets of miR-892b were identified and verified by overexpression of synthetic miRNA mimics and luciferase assays. Cross-talk between Kruppel-like factor 10 (KLF10) and Indian hedgehog (Ihh) was investigated using KLF10 knockdown (KD). miR-892b enhanced chondrogenic makers and suppressed hypertrophy in hMSC chondrogenesis, mimicking parathyroid hormone-related peptide (PTHrP). KLF10, a transcription factor and miR-892b target, directly regulated Ihh promoter activity. Like miR-892b, KLF10 KD enhanced hMSC chondrogenesis and inhibited hypertrophy. Our findings suggest a key role of miR-892b in targeting the KLF10-Ihh axis as a regulator of hypertrophy in TGF-beta-mediated chondrogenesis of hMSCs and provide a novel strategy for preventing hypertrophy in chondrogenesis from MSCs. CI - Copyright (c) 2019 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Lee, Jong Min AU - Lee JM AD - Research Institute for Integrative Regenerative Biomedical Engineering, Dongguk University, Goyang 10326, Republic of Korea. FAU - Ko, Ji-Yun AU - Ko JY AD - Research Institute for Integrative Regenerative Biomedical Engineering, Dongguk University, Goyang 10326, Republic of Korea. FAU - Kim, Hye Young AU - Kim HY AD - Research Institute for Integrative Regenerative Biomedical Engineering, Dongguk University, Goyang 10326, Republic of Korea. FAU - Park, Jeong-Won AU - Park JW AD - Research Institute for Integrative Regenerative Biomedical Engineering, Dongguk University, Goyang 10326, Republic of Korea. FAU - Guilak, Farshid AU - Guilak F AD - Department of Orthopaedic Surgery, Washington University and Shriners Hospitals for Children-St. Louis, St. Louis, MO 63110, USA. FAU - Im, Gun-Il AU - Im GI AD - Research Institute for Integrative Regenerative Biomedical Engineering, Dongguk University, Goyang 10326, Republic of Korea. Electronic address: imgunil@hanmail.net. LA - eng PT - Journal Article DEP - 20190613 PL - United States TA - Mol Ther Nucleic Acids JT - Molecular therapy. Nucleic acids JID - 101581621 PMC - PMC6612925 OTO - NOTNLM OT - KLF10 OT - chondrogenesis OT - hypertrophy OT - mesenchymal stem cells OT - miR-892b EDAT- 2019/07/10 06:00 MHDA- 2019/07/10 06:01 PMCR- 2019/06/13 CRDT- 2019/07/09 06:00 PHST- 2018/11/08 00:00 [received] PHST- 2019/05/16 00:00 [revised] PHST- 2019/05/31 00:00 [accepted] PHST- 2019/07/10 06:00 [pubmed] PHST- 2019/07/10 06:01 [medline] PHST- 2019/07/09 06:00 [entrez] PHST- 2019/06/13 00:00 [pmc-release] AID - S2162-2531(19)30162-3 [pii] AID - 10.1016/j.omtn.2019.05.029 [doi] PST - ppublish SO - Mol Ther Nucleic Acids. 2019 Sep 6;17:310-322. doi: 10.1016/j.omtn.2019.05.029. Epub 2019 Jun 13.