Department of Orthopedics, The First Hospital of China Medical University, Shenyang, Liaoning, China.
Department of Orthopedics, The Fourth Hospital of China Medical University, Shenyang, Liaoning, China.
Biochem Biophys Res Commun. 2019 Jun 11;513(4):883-890. doi: 10.1016/j.bbrc.2019.04.030. Epub 2019 Apr 16.
Type 2 diabetes osteoporosis has recently become a hot topic in the study of diabetic complications, but the specific mechanism of its development remains unclear. Non-imprinted in Prader-Willi/Angelman syndrome region protein 2 (NIPA2), a highly-selective magnesium ion transporter, has been found to be associated with type 2 diabetes. In this study we aimed to investigate the specific role and mechanism of NIPA2 in the pathogenesis of type 2 diabetes osteoporosis. We first used western blotting, PCR, immunofluorescence, and magnesium ion probes to detect changes of NIPA2 and intracellular magnesium levels in osteoblasts at different concentrations of advanced glycation end products (AGEs). We then up- or down-regulated NIPA2 using a lentivirus and analyzed apoptotic biomarkers as well as the osteogenic ability of osteoblasts. We found that AGEs dose-dependently down-regulated the expression of NIPA2 in osteoblasts. NIPA2 also regulated osteoblast apoptosis by affecting the intracellular magnesium level and further affecting the osteogenic capacity of osteoblasts. Our study revealed the changes of NIPA2 in response to AGEs in the environment, as well as its function and mechanism in osteoblasts, demonstrating its important role in the pathogenesis of type 2 diabetes osteoporosis. The study suggests that NIPA2 is a potential target for the treatment of type 2 diabetes osteoporosis.
2 型糖尿病骨质疏松症最近成为糖尿病并发症研究的热点，但具体的发病机制仍不清楚。非印记 Prader-Willi/Angelman 综合征区域蛋白 2（NIPA2）是一种高度选择性的镁离子转运蛋白，已被发现与 2 型糖尿病有关。在本研究中，我们旨在研究 NIPA2 在 2 型糖尿病骨质疏松症发病机制中的具体作用和机制。我们首先使用 Western blot、PCR、免疫荧光和镁离子探针检测不同浓度糖基化终产物（AGEs）作用下成骨细胞中 NIPA2 和细胞内镁水平的变化。然后，我们使用慢病毒上调或下调 NIPA2，并分析成骨细胞的凋亡生物标志物和成骨能力。我们发现 AGEs 呈剂量依赖性地下调成骨细胞中 NIPA2 的表达。NIPA2 还通过影响细胞内镁水平进而影响成骨细胞的成骨能力来调节成骨细胞凋亡。我们的研究揭示了 NIPA2 对环境中 AGEs 的反应变化及其在成骨细胞中的功能和机制，表明其在 2 型糖尿病骨质疏松症发病机制中的重要作用。该研究提示 NIPA2 可能成为治疗 2 型糖尿病骨质疏松症的潜在靶点。
