Long non-coding RNA HCAR promotes endochondral bone repair by upregulating VEGF and MMP13 in hypertrophic chondrocyte through sponging miR-15b-5p

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 factorα(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.