长非编码 RNA 同源盒 D 基因簇反义生长相关长非编码 RNA/微小 RNA-182-5p/同源盒蛋白 A10 通过加速骨髓间充质干细胞成骨分化缓解绝经后骨质疏松症。

BACKGROUND: Studies have illuminated that long non-coding RNA (lncRNA) influences bone cell differentiation and formation. Nevertheless, whether lncRNA Homeobox D gene cluster antisense growth-associated long noncoding RNA (HAGLR) was implicated in postmenopausal osteoporosis (PMOP) was yet uncertain. PURPOSE: The research was to explore HAGLR's role in the osteogenic differentiation (OD) process of bone marrow mesenchymal stem cells (BMSCs). METHODS: BMSCs were isolated from mouse bone marrow tissues and identified by electron microscope and flow cytometry. HAGLR, microRNA (miR)-182-5p, and homeobox protein A10 (Hoxa10) levels in BMSCs were detected. Mouse BMSC OD process was induced, and calcium deposition and alkaline phosphatase content were analyzed, as well as expressions of runt-related transcription factor 2, osteopontin, and osteocalcin, and cell apoptosis. Bilateral ovaries were resected from mice to construct the ovariectomized model and bone mineral density, maximum bending stress, maximum load, and elastic modulus of the femur were tested, and the femur was histopathologically evaluated. Chondrocyte apoptosis in the articular cartilage of mice was analyzed. Analysis of the interaction of HAGLR, miR-182-5p with Hoxa10 was conducted. RESULTS: HAGLR and Hoxa10 were down-regulated and miR-182-5p was elevated in PMOP patients. During the BMSC OD process, HAGLR and Hoxa10 levels were suppressed, while miR-182-5p was elevated. Promotion of HAGLR or suppression of miR-182-5p accelerated OD of BMSCs. Inhibition of miR-182-5p reversed the inhibitory effect of HAGLR on BMSC OD. In in vivo experiments, up-regulating HAGLR alleviated PMOP, while silencing Hoxa10 reversed the effects of upregulating HAGLR. HAGLR performed as a sponge for miR-182-5p, while miR-182-5p targeted Hoxa10. CONCLUSION: In general, HAGLR boosted the OD process of BMSCs and relieved PMOP via the miR-182-5p/Hoxa10 axis. These data preliminarily reveal the key role of HAGLR in PMOP, and the research results have a certain reference for the treatment of PMOP.

背景：研究表明，长非编码 RNA（lncRNA）影响骨细胞分化和形成。然而，长非编码 RNA 同源盒 D 基因簇反义生长相关长非编码 RNA（HAGLR）是否参与绝经后骨质疏松症（PMOP）尚不确定。

目的：本研究旨在探讨 HAGLR 在骨髓间充质干细胞（BMSCs）成骨分化（OD）过程中的作用。

方法：从鼠骨髓组织中分离 BMSCs，通过电子显微镜和流式细胞术进行鉴定。检测 BMSCs 中 HAGLR、微小 RNA（miR）-182-5p 和同源盒蛋白 A10（Hoxa10）的水平。诱导小鼠 BMSC OD 过程，分析钙沉积和碱性磷酸酶含量，以及 runt 相关转录因子 2、骨桥蛋白和骨钙素的表达和细胞凋亡。切除小鼠双侧卵巢构建去卵巢模型，测试股骨骨密度、最大弯曲应力、最大载荷和弹性模量，并对股骨进行组织病理学评估。分析小鼠关节软骨中的软骨细胞凋亡。分析 HAGLR、miR-182-5p 与 Hoxa10 的相互作用。

结果：PMOP 患者中 HAGLR 和 Hoxa10 下调，miR-182-5p 上调。在 BMSC OD 过程中，HAGLR 和 Hoxa10 水平受到抑制，而 miR-182-5p 水平升高。促进 HAGLR 或抑制 miR-182-5p 加速 BMSCs 的 OD。在体内实验中，上调 HAGLR 可缓解 PMOP，而沉默 Hoxa10 可逆转上调 HAGLR 的作用。HAGLR 作为 miR-182-5p 的海绵，而 miR-182-5p 靶向 Hoxa10。

结论：综上所述，HAGLR 通过 miR-182-5p/Hoxa10 轴促进 BMSCs 的 OD 过程，缓解 PMOP。这些数据初步揭示了 HAGLR 在 PMOP 中的关键作用，为 PMOP 的治疗提供了一定的参考。