Advanced glycation endproducts interfere with integrin-mediated osteoblastic attachment to a type-I collagen matrix
Advanced glycation endproducts interfere with integrin-mediated osteoblastic attachment to a type-I collagen matrix
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DOI：
10.1016/j.biocel.2003.09.006
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发表时间：
2004-05-01
影响因子：
4
通讯作者：
Cortizo, AM
中科院分区：
文献类型：
--
作者：
McCarthy, AD;Uemura, T;Cortizo, AM
成骨细胞与骨细胞外基质（其中 I 型胶原蛋白占 >85%）的粘附可以调节其生理学的各个方面，例如生长、分化和矿化。在这项研究中，我们检测了 UMR106 大鼠成骨细胞样细胞与对照 (Col) 或高级糖基化终产物修饰 (AGEs-Col) I 型胶原基质的粘附。我们通过将这些细胞与β肽（整合素β亚基的保守序列113-125）或其他两种肽RGD（Arg-Gly-Asp）和DGEA（Asp-Gly-Glu-Ala）（它们是α亚基的识别序列）共孵育，研究了不同整合素受体在成骨细胞粘附中的可能作用。 α(1,5)β(1) 和 α(2)β(1) 整合素。胶原蛋白糖化抑制 UMR106 成骨细胞与基质的粘附（与 Col 相比减少 40%，P < 0.001）。 β-肽对粘附表现出剂量和糖基化依赖性抑制作用，并且在 100 μM 浓度下，可降低 UMR106 细胞对两种基质的粘附（Col 为 42%，P < 0.001；AGEs-Col 为 25%，P < 0.01）。合成肽RGD (1 mM)和DGEA (5 mM)抑制UMR106细胞与Col的附着(分别为30%和20%，P<0.01和P<0.001)，但不抑制与AGEs-Col的附着。 β-肽诱导 UMR106 细胞聚集增加和细胞扩散减少，而 DGEA 则增加细胞在多个方向上延伸的扩散。这些结果表明，α和β整合素亚基可能通过α(1,5)β(1)和α(2)β(1)整合素参与成骨细胞对I型胶原的附着。 I 型胶原蛋白的 AGE 修饰会损害整联蛋白介导的成骨细胞与基质的粘附，因此可能导致糖尿病骨质减少的发病机制。 (C) 2003 Elsevier Ltd. 保留所有权利。
The adhesion of osteoblasts to bone extracellular matrix, of which type-I collagen constitutes >85%, can modulate diverse aspects of their physiology such as growth, differentiation and mineralisation. In this study we examined the adhesion of UMR106 rat osteoblast-like cells either to a control (Col) or advanced-glycation-endproduct-modified (AGEs-Col) type I collagen matrix. We investigated the possible role of different integrin receptors in osteoblastic adhesion, by co-incubating these cells either with beta-peptide (conserved sequence 113-125 of the beta subunit of integrins) or with two other peptides, RGD (Arg-Gly-Asp) and DGEA (Asp-Gly-Glu-Ala), which are recognition sequences for the alpha-subunits Of alpha(1,5)beta(1) and alpha(2)beta(1) integrins. Collagen glycation inhibited the adhesion of UMR106 osteoblasts to the matrix (40% reduction versus Col, P < 0.001). beta-Peptide showed a dose- and glycation-dependent inhibitory effect on adhesion, and at a concentration of 100 muM decreased the attachment of UMR106 cells to both matrices (42% to Col, P < 0.001; and 25% to AGEs-Col, P < 0.01). The synthetic peptides RGD (I mM) and DGEA (5 mM) inhibited the attachment of UMR106 cells to Col (30 and 20%, P < 0.01 and P < 0.001, respectively), but not to AGEs-Col. beta-Peptide induced an increase in UMR106 cell clumping and a decrease in cellular spreading, while DGEA increased spreading with cellular extensions in multiple directions. These results indicate that both alpha and beta integrin subunits participate in osteoblastic attachment to type-I collagen, probably through the alpha(1,5)beta(1) and alpha(2)beta(1) integrins. AGEs-modification of type-I collagen impairs the integrin-mediated adhesion of osteoblastic cells to the matrix, and could thus ' contribute to the pathogenesis of diabetic osteopenia. (C) 2003 Elsevier Ltd. All rights reserved.