lncRNA AC132872.2上调BMP7促骨髓间充质干细胞成骨分化抗骨质疏松发病的机制研究

骨质疏松（OP）发病率高、易致骨折，骨髓间充质干细胞（BMSC）成骨分化在其发病过程起重要作用。LncRNA AC132872.2（lncR-AC ）调控BMSC成骨分化，但机制不清。前期研究发现，OP患者血浆lncR-AC 、BMP7低表达，miRNA-637高表达；miRNA-637是lncR-AC 以及成骨基因BMP7的共同靶点；沉默lncR-AC 后，miRNA-637表达上调，BMP7表达下调；提示lncR-AC 可能通过抑制miRNA-637促进BMP7表达，促进BMSC成骨分化。据此，本项目拟采用双荧光素酶报告实验、RIP等多种分子互作实验以及分子生物实验验证lncR-AC 与miRNA-637的互作关系，阐明lncRNA通过miRNA调控调BMP7促进BMSC成骨分化的详细分子机制，揭示lncRNA AC132872.2调控OP发病的机制，为OP的诊治奠定理论基础。

Osteoporosis(OP) is a skeletal disease characterized by high incidence, and it’s common for leading to fractures. The osteogenic differentiation of bone marrow mesenchymal stem cells (BMSC) plays an crucial role in its pathogenesis. LncRNA AC132872.2 (lncR-AC) is able to regulate the osteogenic differentiation of BMSC, however, the mechanism remains unclear. Our previous study has found that LncRNA AC132872.2 and BMP7 is down-regulated in OP patients’ plasma, while miRNA-637 is up-regulated. And bioinformatics analysis finding shows that both lncRNA AC132872.2 and osteogenesis gene BMP7 can target miRNA-637. After silencing lncRNA AC132872.2, the expression of miRNA-637 is up-regulated and BMP7 is down-regulated. Thus, we hypothesized that lncRNA AC132872.2 may promotes the osteogenic differentiation of BMSC by inhibiting the expression of miRNA-637 and up-regulating BMP7. Based on this, the project intends to use molecular interaction experiments like dual luciferase reporter assay, RIP etc., and molecular biological experiments to verify the interaction between LncRNA AC132872.2 and miRNA-637, to clarify the detailed mechanism of that lncRNA regulating BMP7 by targeting the miRNA and promoting the osteogenic differentiation of BMSC. Furthermore, revealing the mechanism of LncRNA AC132872.2 regulating the pathogenesis of OP and providing theoretical basis for the diagnosis and treatment of OP.