LncRNA H19/miRNA-21a-5p信号通路在BMP2调控发育性髋关节发育不良的髋臼软骨内骨化中的作用及分子机制

发育性髋关节发育不良（DDH）的髋臼软骨内骨化明显延迟，因此调控软骨内骨化对治疗DDH具有重要价值。BMP2具有诱导软骨内骨化的重要作用。申请人前期研究发现H19具有调控BMP2诱导的软骨内骨化作用，当前实验证实这与miRNA-21a-5p相关。提出基于H19/miRNA-21a-5p调控BMP2诱导软骨内成骨用于治疗DDH髋臼软骨内骨化延迟的科学假设。本课题旨在前期研究的基础上，通过构建表达BMP2和沉默H19的软骨细胞及制备肥大软骨细胞内敲出H19的小鼠DDH模型，采用原位杂交、免疫组化、基因芯片等技术检测H19/miRNA-21a-5p对BMP2诱导的软骨内骨化是否具有调控作用及对DDH髋臼软骨内骨化的作用，从而阐明H19/miRNA-21a-5p调控BMP2诱导的软骨内骨化对DDH的修复作用。这不仅为DDH髋臼发育机制研究提供了新的视点，同时为针对DDH早期治疗的药物研制奠定基础。

Acetabular endochondral ossification in developmental dysplasia of hip (DDH) is significantly delayed, so the regulation of endochondral ossification is of great value in the treatment of DDH. Current studies have confirmed that BMP2 plays an important role in inducing chondrocyte hypertrophy and endochondral ossification. The applicant found that H19 can regulate the hypertrophic differentiation of chondrocyte and endochondral ossification induced by BMP2, which reported in our previous study, and the current experiment preliminarily confirmed that this is related to miRNA-21a-5p. Therefore, we propose a scientific hypothesis that endochondral ossification induced by BMP2 is regulated by H19/miRNA-21a-5p, to which treat delayed acetabular ossification in DDH. On the basis of previous studies, the purpose of this study was to establish a mouse DDH model of H19 conditional knockout in hypertrophic chondrocytes and to construct chondrocytes stably expressing BMP2 and silencing H19 expression. In situ hybridization, immunohistochemistry and gene chip were used to detect the regulation of H19/miRNA-21a-5p signal pathway on BMP2-induced endochondral ossification and acetabular endochondral ossification of DDH. This will elucidate the role of H19/miRNA-21a-5p signaling pathway in regulating the repair of BMP2-induced endochondral ossification on acetabular dysplasia in DDH. This not only provides a new perspective for the study of the mechanism of acetabular development in DDH, but also lays a solid foundation for the research and development of drugs for early treatment of DDH.