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 CD31^hiEmcn^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.

软骨内成骨是骨修复的重要途径。尽管新出现的证据揭示了长链非编码 RNA (lncRNA) 在骨骼和软骨发育中的功能，但 lncRNA 在软骨内骨修复中的作用仍然很大程度上未知。在这里，我们鉴定了一种 lncRNA，命名为肥大软骨细胞血管生成相关 lncRNA (HCAR)，并证明它通过上调肥大软骨细胞中基质金属肽酶 13 (Mmp13) 和血管内皮生长因子 α (Vegfa) 的表达来促进软骨内骨修复. 肥大软骨细胞中的 Lnc-HCAR 敲低抑制了软骨基质重塑并降低了 CD31 ^hi Emcn ^hi骨修复模型中的血管数量。在机制上，我们通过荧光原位杂交（FISH）测定证明lnc-HCAR主要富集在细胞质中，并且它充当了miR-15b-5p的分子海绵。此外，在肥大的软骨细胞中，lnc-HCAR 与 miR-15b-5p 竞争性结合以增加 Vegfa 和 Mmp13 的表达。我们的研究结果证明lncRNA深入参与软骨内骨修复，这将为未来促进骨折愈合的策略提供新的理论基础。