Long non-coding RNA HCAR promotes endochondral bone repair by upregulating VEGF and MMP13 in hypertrophic chondrocyte through sponging miR-15b-5p.
Genes Dis
; 9(2): 456-465, 2022 Mar.
Article
em En
| MEDLINE
| ID: mdl-35224160
ABSTRACT
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 α (Vegfa) in hypertrophic chondrocytes. Lnc-HCAR knockdown in hypertrophic chondrocytes restrained the cartilage matrix remodeling and decrease the CD31hiEmcnhi 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.
BMSCs, bone marrow mesenchymal stem cells; Bone marrow mesenchymal stem cells; Bone repair; Chondrocyte; Enchondral bone repair; HCAR, hypertrophic chondrocyte angiogenesis-related lncRNA; Hoxa2, homeobox A2; Long non coding RNA; Mef2c, myocyte enhancer factor 2C; Mmp13, matrix metallopeptidase 13; OA, osteoarthritis; Osx, osterix; Runx2, runt-related transcription factor 2; Vegfa, vascular endothelial growth factor α; lncRNA, long no-coding RNA
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Genes Dis
Ano de publicação:
2022
Tipo de documento:
Article