Effects of advanced glycation end products on osteocytes mechanosensitivity
Effects of advanced glycation end products on osteocytes mechanosensitivity
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晚期糖基化终末产物对骨细胞机械敏感性的影响
DOI：
10.1016/j.bbrc.2021.06.074
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发表时间：
2021
影响因子：
3.1
通讯作者：
Fan Yu-Bo
中科院分区：
文献类型：
--
作者：
Yang Xiao;Liu Cong-Jin;Wang Zhen-Zhen;Ding Dong;Shi Jing-Wen;Wu Xin-Tong;Sun Lian-Wen;Fan Yu-Bo
骨细胞对机械载荷极为敏感，控制着骨重建过程。晚期糖基化终末产物(AGEs)具有诱导骨细胞凋亡的能力。为探讨AGEs对成骨细胞力学敏感性的影响，用低浓度(50μg/ml)和高浓度(400μg/ml)的AGEs处理骨样细胞(MLO-Y4)1d，暴露于15dyne/cm2的流体剪应力下。检测F-肌动蛋白细胞骨架、前列腺素E_2(PGE_2)、一氧化氮(NO)、WNT/β-连环蛋白信号通路活性m RNA表达变化，检测骨钙素、核因子-kappaB受体激活剂配体/骨保护素对骨细胞骨重建功能的调节作用。结果表明，AGEs的积聚抑制了骨细胞对机械载荷的感觉，促进了剪切诱导的NO和PGE_2的释放，抑制了Wnt/β-catenin信号通路的机械敏感性，进而促进了OCN和RANKL/OPG mRNA的表达。提示AGEs对骨细胞的力学敏感性有不利影响，导致骨细胞在机械刺激下对骨重建过程的调控产生负面影响。这项工作为解释骨细胞机械敏感性的改变机制提供了新的视角，为探讨骨质疏松的机制提供了新的线索。
Osteocytes are extremely sensitive to mechanical loading and govern bone remodeling process. Advanced glycation end products (AGEs) have the capacity to induce osteocyte apoptosis. In order to investigate the effects of AGEs on the mechanosensitivity of osteocytes, the osteocytic-like cells (MLO-Y4) were treated with low (50 μg/ml) and high (400 μg/ml) concentrations of AGEs for 1day and exposed to 15 dyne/cm2of fluid shear stress. Then the F-actin cytoskeleton, prostaglandin E2(PGE2), Nitric oxide (NO), the Wnt/β-catenin signaling pathway activity mRNA expressions were detected for osteocytes mechanical response changes; osteocalcin (OCN) and receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin (OPG) were detected for the regulation on bone remodeling function of osteocytes. The results showed that AGEs accumulation inhibited the sense of osteocytes to external mechincal loading, promoted shear-induced NO and PGE2 release, suppressed the mechanosensitivity of Wnt/β-catenin signaling pathway, and furthermore promoted OCN and RANKL/OPG mRNA expressions. These indicated AGEs had an adverse impact on the mechanosensitivity of osteocytes, and led to a negative effect on their regulation of bone remodeling process under mechanical stimulation. This work provides a new perspective to interpret the alteration mechanism of osteocytes mechanosensitivity and provides a novel clue for exploring the mechanism of osteoporosis.