PMID- 35224160 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220301 IS - 2352-3042 (Electronic) IS - 2352-4820 (Print) IS - 2352-3042 (Linking) VI - 9 IP - 2 DP - 2022 Mar TI - Long non-coding RNA HCAR promotes endochondral bone repair by upregulating VEGF and MMP13 in hypertrophic chondrocyte through sponging miR-15b-5p. PG - 456-465 LID - 10.1016/j.gendis.2020.07.013 [doi] AB - Endochondral bone formation is an important route for bone repair. Although emerging evidence has revealed the functions of long non-coding RNAs (lncRNAs) in bone and cartilage development, the effect of lncRNAs in endochondral bone repair is still largely unknown. Here, we identified a lncRNA, named Hypertrophic Chondrocyte Angiogenesis-related lncRNA (HCAR), and proved it to promote the endochondral bone repair by upregulating the expression of matrix metallopeptidase 13 (Mmp13) and vascular endothelial growth factor alpha (Vegfa) in hypertrophic chondrocytes. Lnc-HCAR knockdown in hypertrophic chondrocytes restrained the cartilage matrix remodeling and decrease the CD31(hi)Emcn(hi) vessels number in a bone repair model. Mechanistically, we proved that lnc-HCAR was mainly enriched in the cytoplasm using fluorescence in situ hybridization (FISH) assay, and it acted as a molecular sponge for miR-15b-5p. Further, in hypertrophic chondrocytes, lnc-HCAR competitively bound to miR-15b-5p to increase Vegfa and Mmp13 expression. Our results proved that lncRNA is deeply involved in endochondral bone repair, which will provide a new theoretical basis for future strategies for promoting fracture healing. CI - (c) 2021 Chongqing Medical University. Production and hosting by Elsevier B.V. FAU - Bai, Yun AU - Bai Y AD - Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Chongqing 400038, PR China. FAU - Gong, Xiaoshan AU - Gong X AD - Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Chongqing 400038, PR China. FAU - Dong, Rui AU - Dong R AD - Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Chongqing 400038, PR China. FAU - Cao, Zhen AU - Cao Z AD - Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Chongqing 400038, PR China. FAU - Dou, Ce AU - Dou C AD - Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Chongqing 400038, PR China. FAU - Liu, Chuan AU - Liu C AD - Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Chongqing 400038, PR China. AD - Institute of Trauma Orthopedics, Army General Hospital of PLA, Beijing 100700, PR China. FAU - Li, Jianmei AU - Li J AD - Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Chongqing 400038, PR China. FAU - Kang, Fei AU - Kang F AD - Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Chongqing 400038, PR China. FAU - Dai, Jingjin AU - Dai J AD - Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Chongqing 400038, PR China. FAU - Zhao, Chunrong AU - Zhao C AD - Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Chongqing 400038, PR China. FAU - Tian, Zhansong AU - Tian Z AD - Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Chongqing 400038, PR China. FAU - Tan, Jiulin AU - Tan J AD - Department of Orthopedics, Southwest Hospital, Third Military Medical University, Chongqing 400038, PR China. FAU - Dai, Qijie AU - Dai Q AD - Department of Orthopedics, Southwest Hospital, Third Military Medical University, Chongqing 400038, PR China. FAU - Dong, Shiwu AU - Dong S AD - Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Chongqing 400038, PR China. AD - Department of Orthopedics, Southwest Hospital, Third Military Medical University, Chongqing 400038, PR China. AD - State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing 400038, PR China. LA - eng PT - Journal Article DEP - 20200810 PL - Netherlands TA - Genes Dis JT - Genes & diseases JID - 101635967 PMC - PMC8843884 OTO - NOTNLM OT - BMSCs, bone marrow mesenchymal stem cells OT - Bone marrow mesenchymal stem cells OT - Bone repair OT - Chondrocyte OT - Enchondral bone repair OT - HCAR, hypertrophic chondrocyte angiogenesis-related lncRNA OT - Hoxa2, homeobox A2 OT - Long non coding RNA OT - Mef2c, myocyte enhancer factor 2C OT - Mmp13, matrix metallopeptidase 13 OT - OA, osteoarthritis OT - Osx, osterix OT - Runx2, runt-related transcription factor 2 OT - Vegfa, vascular endothelial growth factor alpha OT - lncRNA, long no-coding RNA EDAT- 2020/08/10 00:00 MHDA- 2020/08/10 00:01 PMCR- 2020/08/10 CRDT- 2022/02/28 05:40 PHST- 2020/04/16 00:00 [received] PHST- 2020/06/08 00:00 [revised] PHST- 2020/07/30 00:00 [accepted] PHST- 2022/02/28 05:40 [entrez] PHST- 2020/08/10 00:00 [pubmed] PHST- 2020/08/10 00:01 [medline] PHST- 2020/08/10 00:00 [pmc-release] AID - S2352-3042(20)30096-9 [pii] AID - 10.1016/j.gendis.2020.07.013 [doi] PST - epublish SO - Genes Dis. 2020 Aug 10;9(2):456-465. doi: 10.1016/j.gendis.2020.07.013. eCollection 2022 Mar.