Fisher J E, Caulfield M P, Sato M, Quartuccio H A, Gould R J, Garsky V M, Rodan G A, Rosenblatt M
Department of Bone Biology and Osteoporosis, Merck Research Laboratories, West Point, Pennsylvania 19486.
Endocrinology. 1993 Mar;132(3):1411-3. doi: 10.1210/endo.132.3.8440195.
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 beta 3) 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.
破骨细胞介导的骨吸收需要在破骨细胞与矿化骨基质之间形成一个紧密密封的隔室。这个隔室起到细胞外“溶酶体”的作用，其中含有蛋白水解酶和酸。破骨细胞表面展示的玻连蛋白受体（VnR，整合素αvβ3）可能在破骨细胞与吸收表面的附着过程中发挥作用。已知VnR能与含精氨酰 - 甘氨酰 - 天冬氨酸（RGD）的基质蛋白结合，最近有报道称含RGD序列的可溶性肽可在体外阻断破骨细胞与骨的附着并抑制骨吸收。在本研究中，echistatin（一种含有RGD序列基序的天然存在的蛋白质）在体内被证明能完全抑制破骨细胞介导的骨吸收。Echistatin或更小的衍生肽可能在治疗以骨吸收过多为特征的疾病（如骨质疏松症和转移性骨病）中有用。
