ARG-GLY-ASP (RGD) PEPTIDES AND THE ANTI-VITRONECTIN RECEPTOR ANTIBODY 23C6 INHIBIT DENTIN RESORPTION AND CELL SPREADING BY OSTEOCLASTS
ARG-GLY-ASP (RGD) PEPTIDES AND THE ANTI-VITRONECTIN RECEPTOR ANTIBODY 23C6 INHIBIT DENTIN RESORPTION AND CELL SPREADING BY OSTEOCLASTS
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DOI：
10.1016/0014-4827(91)90386-9
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发表时间：
1991-08-01
影响因子：
3.7
通讯作者：
HELFRICH, MH
中科院分区：
文献类型：
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作者：
HORTON, MA;TAYLOR, ML;HELFRICH, MH
使用针对人、大鼠和鸡玻连蛋白受体αVβ3组分的一系列单克隆和多克隆抗血清进行研究，用单克隆抗体23 C6进行的生化分析证实了鸡破骨细胞上存在大小相似的玻连蛋白受体异源二聚体（110 - 95 kDa减少）的免疫沉淀从人成骨细胞瘤巨细胞。与纤维连接蛋白中的细胞粘附序列相对应的合成肽GRGDSP，而不是GRGESP肽，诱导了显著的鸡和大鼠破骨细胞在IC 50 s（±SEM）分别为210.0±14.4和191.4±13.7 μM时，破骨细胞收缩（P< 0.005）;抗玻连蛋白受体αVβ3复合物单克隆抗体23 C6对鸡破骨细胞也产生类似的变化（IC 50= 1.45±0.22 μM）。抗体23 C6在4.4至88 μg/ml的浓度范围内抑制小鸡破骨细胞在牙本质中吸收的小窝数量;在88 μg/ml（6 μM）的最终浓度下观察到显著减少76%（P= 0.03）。肽对牙本质吸收的影响不太明显。使用鸡破骨细胞没有观察到一致的抑制。然而，观察到大鼠破骨细胞对吸收的抑制作用;在400 μM肽浓度下，GRGDSP（78%; P< 0.01）和GRGESP（67%; P= 0.02）肽均显著降低吸收。这些数据表明，破骨细胞功能可以被低浓度的抗玻连蛋白受体抗体23 C6破坏。本研究中使用的肽的抑制作用对牙本质再吸收产生了影响，其通常较弱且可变，尽管破骨细胞粘附以精氨酸-甘氨酸-天冬氨酸（RGD）依赖性方式始终受到抑制。我们的结论是玻连蛋白受体可能发挥重要作用，影响破骨细胞的矿化组织的再吸收。
Studies with a range of monoclonal and polyclonal antisera to components of the human, rat, and chick vitronectin receptor, αVβ3, and the VLA β1 chain show that chick and rat osteoclasts express similar integrin receptors to those described in man. Biochemical analysis with monoclonal antibody 23C6 confirmed the presence on chick osteoclasts of a vitronectin receptor heterodimer of similar size (110 95 kDa reduced) to that immunoprecipitated from human osteoclastoma giant cells. The synthetic peptide GRGDSP, corresponding to the cell adhesion sequence in fibronectin, but not GRGESP peptide, induced significant (P< 0.005) osteoclast retraction in chick and rat osteoclasts at IC 50 s (±SEM) of 210.0±14.4 and 191.4±13.7 μM, respectively; monoclonal anti-vitronectin receptor αVβ3 complex antibody, 23C6, produced similar changes in chick osteoclasts (IC 50= 1.45±0.22 μM). Antibody 23C6 inhibited the number of pits resorbed in dentine by chick osteoclasts over a concentration range of 4.4 to 88 μg/ml; a significant 76% reduction (P= 0.03) was observed at a final concentration of 88 μg/ml (6 μM). The effect of peptides upon dentine resorption was less dramatic. No consistent inhibition was seen using chick osteoclasts. Inhibitory effects on resorption by rat osteoclasts were, however, observed; significant reduction in resorption occurred with both GRGDSP (78%; P< 0.01) and GRGESP (67%; P= 0.02) peptides at 400 μM peptide concentration. These data demonstrate that osteoclast function can be disrupted by low concentrations of the anti-vitronectin receptor antibody, 23C6. The inhibitory effects of the peptides used in this study produced effects on dentine resorption which were generally weaker and variable, although osteoclast cell adhesion was consistently inhibited in an Arg Gly Asp (RGD)-dependent manner. We conclude that the vitronectin receptor may play an important role in effecting resorption of mineralized tissues by osteoclasts.