高葡萄糖和碳氧甲基氨酸对骨细胞基因表达的影响
Rachana Vaidya1,2, Lauren Conlon1, Olivia Duclos1
1Department of Bioengineering, University of Massachusetts Dartmouth, Dartmouth, MA, USA.
概括
高葡萄糖条件破坏骨细胞功能,改变骨重塑和炎症. 像CML这样的高级糖化终端产品 (AGEs) 激活特定的途径,突出显示糖尿病骨脆弱性的AGE-RAGE轴.
科学领域:
- 生物化学 生化学
- 细胞生物学 细胞生物学
- 内分泌学 在内分泌学.
背景情况:
- 糖尿病与骨脆弱有关,即使骨矿物质密度正常.
- 先进的糖化终产物 (AGEs) 积聚在骨中,通过AGE (RAGE) 的受体损害骨细胞功能.
研究的目的:
- 研究高葡萄糖 (HG) 和碳糖甲基氨酸 (CML) 对骨细胞骨重塑,糖化,炎症和细胞功能的影响.
- 阐明 AGE-RAGE轴在糖尿病骨脆弱性中的作用.
主要方法:
- 用高葡萄糖 (30毫米) 或CML (3微米) 治疗的小鼠骨质细胞系 (OCY454-12H).
- 通过qPCR和功能测试评估了骨改造标记物 (SOST,RANKL,OPG),糖化标记物 (RAGE,AGER1),炎症性细胞因子 (IL-6,TNF-α) 和细胞功能 (增殖,活力,细胞亡).
主要成果:
- 高血糖显著增加了SOST,RANKL,OPG,RAGE,AGER1,IL-6和TNF-α的表达,同时增加了亡.
- 在CML上调调节RAGE和AGER1,但在生理度下没有显著影响骨重塑标记物,炎症细胞因子或细胞功能.
- 在高葡萄糖条件下,RANKL/OPG比率保持不变.
结论:
- 高葡萄糖通过改变骨重塑,糖化和炎症途径来破坏骨细胞功能.
- 在生理层面上,CML可以选择性地激活糖化标记物,而不会导致更广泛的细胞功能障碍.
- AGE-RAGE轴在糖尿病骨脆弱性中至关重要,这表明AGE积累和RAGE信号的治疗点.
更多相关视频
08:28A Lab-On-A-Chip Platform for Stimulating Osteocyte Mechanotransduction and Analyzing Functional Outcomes of Bone Remodeling
Published on: May 21, 2020
6.6K
06:47Isolation of Mesenchymal Stem Cells from Human Alveolar Periosteum and Effects of Vitamin D on Osteogenic Activity of Periosteum-derived Cells
Published on: May 4, 2018
9.3K
相关概念视频
Operons
48.5K
Prokaryotes can control gene expression through operons—DNA sequences consisting of regulatory elements and clustered, functionally related protein-coding genes. Operons use a single promoter sequence to initiate transcription of a gene cluster (i.e., a group of structural genes) into a single mRNA molecule. The terminator sequence ends transcription. An operator sequence, located between the promoter and structural genes, prohibits the operon’s transcriptional activity if bound by...
48.5K
Cell Specific Gene Expression
13.4K
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...
13.4K
cAMP-dependent Protein Kinase Pathways
6.1K
Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
6.1K
