INHIBITION OF OSTEOCLASTIC BONE-RESORPTION INVIVO BY ECHISTATIN, AN ARGINYL-GLYCYL-ASPARTYL (RGD)-CONTAINING PROTEIN
INHIBITION OF OSTEOCLASTIC BONE-RESORPTION INVIVO BY ECHISTATIN, AN ARGINYL-GLYCYL-ASPARTYL (RGD)-CONTAINING PROTEIN
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DOI：
10.1210/en.132.3.1411
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发表时间：
1993-03-01
期刊：
影响因子：
4.8
通讯作者：
ROSENBLATT, M
中科院分区：
文献类型：
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作者：
FISHER, JE;CAULFIELD, MP;ROSENBLATT, M
破骨细胞骨吸收需要在破骨细胞和矿化骨基质之间形成紧密密封的隔室。 这个区室作为细胞外的“溶酶体”发挥作用，其中含有蛋白水解酶和酸。破骨细胞表面的玻连蛋白受体（VnR，整合素α（v）β 3）可能在破骨细胞附着于吸收表面中发挥作用。已知VnR与含N-乙酰-甘氨酰-N-乙酰（RGD）的基质蛋白结合，并且最近报道含有RGD序列的可溶性肽可以阻断破骨细胞与骨的附着并抑制体外骨吸收。在这项研究中，echistatin，一种含有RGD序列基序的天然蛋白质，被证明可以完全抑制体内破骨细胞介导的骨吸收。Echistatin或更小的衍生肽可以证明可用于治疗以过度骨吸收为特征的疾病，例如骨质疏松症和转移性骨疾病。
Osteoclastic bone resorption requires the formation of a tightly sealed compartment between the osteoclast and the mineralized bone matrix. This compartment functions as an extracellular ''lysosome'' which contains proteolytic enzymes and acids. Vitronectin receptors (VnR, integrin alpha(v)beta3) displayed on the osteoclast cell surface may play a role in the attachment of osteoclasts to the resorption surface. VnR are known to bind to arginyl-glycyl-aspartyl (RGD)-containing matrix proteins and it has recently been reported that soluble peptides containing RGD sequences can block osteoclast attachment to bone and inhibit bone resorption in vitro. In this study echistatin, a naturally-occurring protein containing an RGD-sequence motif, was shown to completely inhibit osteoclast-mediated bone resorption in vivo. Echistatin or smaller derivative peptides may prove useful in the treatment of disorders characterized by excess bone resorption, such as osteoporosis and metastatic bone disease.