17β-雌二醇 (E2) 在MC3T3-E1细胞中通过基因组/非基因组途径激活矩阵矿化
Hiraku Suzuki1,2, Yuki Fujiwara1, Winda Ariyani1
1Department of Integrative Physiology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi 371-8511, Gunma, Japan.
International journal of molecular sciences
|May 11, 2024
概括
17β-雌二醇 (E2) 通过雌激素受体 (ERs) 在骨质细胞中促进骨基质矿化. 这一途径涉及p38 MAPK激活,独立于核作用,为骨质疏松症提供了一个新的治疗点.
科学领域:
- 内分泌学 在内分泌学.
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 雌激素对于预防骨质疏松症至关重要.
- 骨质母体矿化对于骨健康至关重要.
- 在骨质母细胞中雌激素的精确信号通路尚未完全理解.
研究的目的:
- 为了阐明17β-雌二醇 (E2) 在骨质母体矿化中的新信号通路.
- 研究雌激素受体 (ER) 和下游信号分子在E2介导作用中的作用.
- 确定增强骨矿物化的潜在治疗点.
主要方法:
- 使用了MC3T3-E1骨质母细胞样细胞.
- 在经过和没有E2处理的血清剥离介质中评估矩阵矿化.
- 使用ERα,ERβ抗剂 (ICI182,780),拉洛西芬和GPER1抑制剂 (G15).
- 使用激活剂和抑制剂 (PMA,SB202190,沃特曼宁) 调查了PKC,p38 MAPK和PI3K信号通路的参与.
主要成果:
- 在MC3T3-E1细胞中,E2显著诱导了矩阵矿化.
- E2效应依赖于ERα和ERβ,但没有受到Raloxifene或G15的显著影响.
- E2激活矿化涉及p38 MAPK通路,并被PMA破坏,但不是PI3K抑制剂.
- 受到E2刺激的条件介质诱导了矿化,这表明涉及PKC抑制的副质信号传递.
结论:
- E2通过ERs激活p38 MAPK,独立于核转录,以促进骨质母体矿化.
- 这种新的途径可能涉及到调节PKC信号的分泌因子.
- 这种E2信号通路代表了具有损坏矩阵矿化特征的疾病的潜在治疗标,例如骨质疏松症.
相关概念视频
01:29The Extracellular Matrix
9.0K
Overview
In order to maintain tissue organization, many animal cells are surrounded by structural molecules that make up the extracellular matrix (ECM). Together, the molecules in the ECM maintain the structural integrity of tissue as well as the remarkable specific properties of certain tissues.
Composition of the Extracellular Matrix
The extracellular matrix (ECM) is commonly composed of ground substance, a gel-like fluid, fibrous components, and many structurally and functionally diverse...
In order to maintain tissue organization, many animal cells are surrounded by structural molecules that make up the extracellular matrix (ECM). Together, the molecules in the ECM maintain the structural integrity of tissue as well as the remarkable specific properties of certain tissues.
Composition of the Extracellular Matrix
The extracellular matrix (ECM) is commonly composed of ground substance, a gel-like fluid, fibrous components, and many structurally and functionally diverse...
9.0K
01:13Cell-matrix's Response to Mechanical Forces
2.6K
In animal cells, the extracellular matrix allows cells within tissues to withstand external stresses and transmits signals from the outside of the cell to the inside. The extracellular matrix is extensive, and its composition varies between different types of tissues. For example, the reticular fibers and ground substance make up the ECM in loose connective tissue, while collagen and bone minerals make up the ECM of bone tissue.
Anchoring junctions mechanically attach a cell to the...
Anchoring junctions mechanically attach a cell to the...
2.6K
01:23Role of Matrix Metalloproteases in Degradation of ECM
2.4K
Matrix metalloproteases (MMPs) are enzymes involved in the hydrolysis of proteins and glycoproteins of the extracellular matrix. MMPs are essential for the migration and proliferation of cells through the dense matrix network, throughout embryonic development, and throughout morphogenesis. The first MMP activity discovered was a collagenase in a tadpole's tail undergoing metamorphosis. The active collagen deposition and modifications lead to the morphogenesis of tadpoles into the adult...
2.4K