A peptidomimetic antagonist of the alpha(v)beta3 integrin inhibits bone resorption in vitro and prevents osteoporosis in vivo
| Autor: | Michael A. Horton, V W Engleman, Steven L. Teitelbaum, Steven L. Settle, F. P. Ross, David W. Griggs, G A Nickols, Peter G. Ruminski |
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| Jazyk: | angličtina |
| Rok vydání: | 1997 |
| Předmět: |
Calcitonin
medicine.medical_specialty Integrins Ovariectomy Osteoporosis Integrin Alpha (ethology) Osteoclasts Platelet Glycoprotein GPIIb-IIIa Complex Bone resorption Bone and Bones In vivo Osteoclast Internal medicine medicine Cell Adhesion Animals Humans Receptors Vitronectin Vitronectin Amino Acids Bone Resorption Cells Cultured biology Chemistry General Medicine medicine.disease Rats Endocrinology medicine.anatomical_structure Dentin biology.protein Calcium Female Peptides Oligopeptides Research Article |
| Popis: | Osteoclastic bone degradation requires intimacy between the matrix and the resorptive cell. While the precise role the integrin alpha(v)beta3 plays in the process is not yet understood, occupancy of the heterodimer by soluble ligand or by blocking antibody effectively inhibits bone resorption in vitro and in vivo, suggesting that alpha(v)beta3 blockade may prevent postmenopausal osteoporosis. Thus, we identified a synthetic chemical peptide mimetic, beta-[2-[[5-[(aminoiminomethyl)amino]-1-oxopentyl]amino]-1-+ ++oxoethyl]amino-3-pyridinepropanoic acid, bistrifluoroacetate (SC56631) based upon the alpha(v)beta3 ligand, Arg-Gly-Asp (RGD), which recognizes the isolated integrin, and its relative, alpha(v)beta5, as effectively as does the natural peptide. The mimetic dampens osteoclastic bone resorption in vitro and in vivo. Most importantly, intravenous administration of the mimetic prevents the 55% loss of trabecular bone sustained by rats within 6 wk of oophorectomy. Histological examination of bones taken from SC56631-treated, oophorectomized animals also demonstrates the compound's bone sparing properties and its capacity to decrease osteoclast number. Thus, an RGD mimetic prevents the rapid bone loss that accompanies estrogen withdrawal. |
| Databáze: | OpenAIRE |
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