General Hospital Novo Mesto, Šmihelska Cesta 1, 8000 Novo Mesto, Slovenia.
Faculty of Pharmacy, University of Ljubljana, Aškerčeva Cesta 7, 1000 Ljubljana, Slovenia.
Int J Mol Sci. 2023 Aug 17;24(16):12895. doi: 10.3390/ijms241612895.
Genome-wide association studies (GWAS) are one of the most common approaches to identify genetic loci that are associated with bone mineral density (BMD). Such novel genetic loci represent new potential targets for the prevention and treatment of fragility fractures. GWAS have identified hundreds of associations with BMD; however, only a few have been functionally evaluated. A locus significantly associated with femoral neck BMD at the genome-wide level is intronic SNP rs17040773 located in the intronic region of the () gene ( = 1.5 × 10). Here, we functionally evaluate the role of in bone remodelling by examining the expression of in human bone and muscle tissues and during the osteogenic differentiation of human primary mesenchymal stem cells (MSCs). The expression of was significantly decreased 2.3-fold in bone tissues and 6.2-fold in muscle tissue from osteoporotic patients as compared to the osteoarthritic and control tissues. Next, we show that the expression of changes during the osteogenic differentiation process of human MSCs. Moreover, the silencing of in human osteosarcoma (HOS) cells reduced expression, suggesting that affects osteogenic differentiation through . Altogether, our results indicate that plays a role in bone physiology and in the development of osteoporosis.
全基因组关联研究 (GWAS) 是鉴定与骨密度 (BMD) 相关的遗传基因座的最常用方法之一。这些新的遗传基因座代表了预防和治疗脆性骨折的新的潜在靶点。GWAS 已经确定了数百个与 BMD 相关的基因座;然而,只有少数几个得到了功能评估。在全基因组水平上与股骨颈 BMD 显著相关的基因座是位于 () 基因内含子区域的内含子 SNP rs17040773( = 1.5 × 10)。在这里,我们通过研究 基因在人类骨和肌肉组织中的表达以及在人原代间充质干细胞 (MSCs) 的成骨分化过程中的表达,来评估 在骨重塑中的作用。与骨关节炎和对照组组织相比,骨质疏松症患者的骨组织中 表达显著降低了 2.3 倍,肌肉组织中降低了 6.2 倍。接下来,我们表明 在人 MSCs 的成骨分化过程中表达发生变化。此外,沉默人骨肉瘤 (HOS) 细胞中的 降低了 表达,表明 通过 影响成骨分化。总之,我们的结果表明 在骨生理学和骨质疏松症的发展中起作用。