基因证据支持mTOR依赖的EIF-4E循环蛋白水平和骨质疏松症之间的因果关系
Ting Cheng1,2,3, Yao-Chen Zhang2,3, Ke-Yi Fan2,3
1Department of Rheumatology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
Advances in therapy
|September 20, 2023
概括
门德尔的随机化分析表明,真核细胞启动因子4E (EIF-4E) 和前臂骨矿物质密度 (BMD) 之间存在因果关系. 这一发现为骨质疏松病原和潜在的治疗点提供了新的见解.
科学领域:
- 遗传学 遗传学 是一个
- 生物化学 生物化学
- 骨科 骨科是指骨科的学科.
背景情况:
- 拉巴胺素 (mTOR) 途径的机械性标对于维持骨质平衡至关重要.
- 骨质疏松症 (OP) 的发展受到骨质稳态的影响,但由于依赖观察性研究,因果关系尚不清楚.
- 了解mTOR依赖蛋白和OP之间的因果关系对于开发有效的治疗方法至关重要.
研究的目的:
- 使用孟德尔随机化 (MR) 调查mTOR依赖循环蛋白和骨质疏松症之间的因果关系.
- 确定特定的mTOR相关蛋白质,这些蛋白质可能对骨矿物质密度 (BMD) 有因果影响,并对OP有所贡献.
主要方法:
- 使用权重中位数 (WM),逆方差权重 (IVW) 和MR-Egger回归进行了门德尔随机化分析.
- 对于mTOR蛋白质的仪器变量是从蛋白质组学-GWAS INTERVAL研究中选择的.
- 分析包括使用科克兰的Q测试,MR-PRESSO和留出一个方法对水平形和异质性的评估.
主要成果:
- 通过IVW分析发现,真核细胞启动因子4E (EIF-4E) 与前臂骨矿物质密度 (FA-BMD) (OR=0.938,95% CI 0.887-0.991,p=0.024) 有因果关系.
- 在其他部位 (大腿部,腰椎,脚跟) 中没有观察到EIF-4E和BMD之间的显著因果关系.
- 进行了进一步的分析,以检测和解决潜在的型和异质性.
结论:
- 门德尔的随机化分析确定了EIF-4E和FA-BMD之间的因果关系.
- 这种关联为骨质疏松症的发病过程提供了新的见解.
- EIF-4E可能是治疗骨质疏松症的潜在治疗点.
更多相关视频
09:37A RANKL-based Osteoclast Culture Assay of Mouse Bone Marrow to Investigate the Role of mTORC1 in Osteoclast Formation
Published on: March 15, 2018
13.2K
06:00Development of a Human Preclinical Model of Osteoclastogenesis from Peripheral Blood Monocytes Co-cultured with Breast Cancer Cell Lines
Published on: September 13, 2017
7.2K
相关概念视频
mTOR Signaling and Cancer Progression
3.8K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.8K
PI3K/mTOR/AKT Signaling Pathway
3.6K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.6K
The Nucleolus
8.9K
The nucleolus is the most prominent substructure of the nucleus. When it was first discovered, it was considered to be an isolated organelle that forms fibrils and granules. In 1931, the relationship between the nucleolus and chromosomes was first described by Heitz. He observed that the appearance and size of nucleolus varies depending on the stage of the cell cycle. He also noticed constricted regions on different chromosomes clustered together at definite cell cycle stages. These regions,...
8.9K
Cell Specific Gene Expression
13.6K
Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
13.6K
Mitogens and the Cell Cycle
6.5K
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.5K
