The osteoclast functional antigen, implicated in the regulation of bone resorption, is biochemically related to the vitronectin receptor.
The osteoclast functional antigen, implicated in the regulation of bone resorption, is biochemically related to the vitronectin receptor.
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与骨吸收调节有关的破骨细胞功能抗原在生化上与玻染素受体有关。
DOI：
10.1083/jcb.109.4.1817
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发表时间：
1989-10
期刊：
影响因子：
--
通讯作者：
Horton M
中科院分区：
文献类型：
--
作者：
Davies J;Warwick J;Totty N;Philp R;Helfrich M;Horton M
我们已经通过免疫学和生物化学方法确定了破骨细胞功能抗原（OFA）的结构。OFA是人和动物破骨细胞中丰富的表面抗原，并且先前已通过单克隆抗体13 C2和23 C6表征，其中之一模拟降钙素对骨细胞骨吸收的抑制活性。通过以下标准，我们表明OFA是细胞外基质受体的整合素家族的成员，并且与先前从胎盘和黑色素瘤细胞分离的玻连蛋白受体（VNR）相同或至少高度相关。免疫沉淀分析表明，破骨细胞和猴肾细胞系Vero的OFA在非还原条件下是140 kD（α链）和85 kD（β链）的异二聚体分子;还原时至少释放一种低分子量（α '）物质（大小约为30 kD），产生120/100 kD二聚体。从破骨细胞和Vero细胞中分离的OFA和从胎盘中纯化的VNR的免疫印迹，用OFA的异源血清和血小板gp 111 a（VNR β链）的单克隆抗体探测，显示OFA和VNR的α链之间的免疫交叉反应性，以及两者使用gp 111 a作为β链。来自Vero细胞的OFA与含Arg-Gly- Asp的肽（GRGDSPPK）结合，分离出由抗OFA单克隆抗体13 C2和23 C6识别的异源二聚体。免疫组织化学分析显示，抗OFA抗体识别的抗原在人体中的组织分布相似，抗黑色素瘤VNR的单克隆抗体LM 142、胎盘VNR的多克隆抗体和推定VNR β链血小板糖蛋白111 a的单克隆抗体。最后，NH 2末端氨基酸测序显示猴α链的氨基末端在12个指定残基中与人VNR α链的氨基末端相同。OFA的β链序列在前18个氨基酸序列中与血小板gp 111 a（VNR β）至少有1个（最多4个）位置不同。这些和其他数据提供了VNR功能的第一个指示，并表明涉及整合素的细胞-细胞和细胞-细胞外基质相互作用可能在骨生理学中起重要作用。
We have defined the structure of the Osteoclast Functional Antigen (OFA) by immunological and biochemical means. OFA is an abundant surface antigen in human and animal osteoclasts and has been characterized previously by monoclonal antibodies 13C2 and 23C6, one of which mimicks the inhibitory activity of calcitonin on osteoclastic bone resorption. By the following criteria we show that OFA is a member of the integrin family of extracellular matrix receptors and is identical, or at least highly related, to the vitronectin receptor (VNR) previously isolated from placenta and melanoma cells. Immunoprecipitation analysis demonstrates that OFA from osteoclasts and a monkey kidney cell line Vero is a heterodimeric molecule of 140 kD (alpha chain) and 85 kD (beta chain) under nonreducing conditions; on reduction at least one low molecular mass (alpha') species (of approximately 30-kD size) is released, resulting in a 120/100-kD dimer. Immunoblots of OFA isolated from osteoclasts and Vero cells and VNR purified from placenta and probed with heterosera to OFA and monoclonal antibodies to platelet gp111a (VNR beta chain) show immunological cross- reactivity between the alpha chains of OFA and VNR and the use of gp111a as a beta chain by both. OFA from Vero cells binds to an Arg-Gly- Asp containing peptide (GRGDSPPK) isolating a heterodimer recognized by anti-OFA monoclonal antibodies, 13C2 and 23C6. Immunohistochemical analysis showed a similar tissue distribution in humans for the antigen recognized by anti-OFA antibodies, a monoclonal antibody, LM142, raised to melanoma VNR, polyclonal antibodies to the placental VNR and a monoclonal antibody to the presumptive VNR beta chain, platelet glycoprotein 111a. Finally, NH2 terminal amino acid sequencing showed that the amino-terminus of the monkey alpha chain was identical in the 12 assigned residues to that of human VNR alpha chain. The beta chain sequence of OFA differed at least 1 (and up to 4) positions from platelet gp111a (VNR beta) in the first 18 amino acids sequenced. These, and other, data provide the first indication of a function for the VNR and suggest that cell-cell and cell-extracellular matrix interactions involving integrins may play an important role in bone physiology.