Inhibition of osteoporosis by the αvβ3 integrin antagonist of rhodostomin variants

Tzu Hung Lin, Rong Sen Yang, Huang Ju Tu, Houng Chi Liou, Yen Ming Lin, Woei-Jer Chuang, Wen Mei Fu

研究成果: Article

4 引文 (Scopus)

摘要

Integrins are heterodimeric cell surface receptors that mediate cell–cell and cell–matrix interaction. The vitronectin and osteopontin receptor αvβ3 integrin has increased expression levels and is implicated in the adhesion, activation, and migration of osteoclasts on the bone surface as well as osteoclast polarization. αvβ3 integrin plays an important role in osteoclast differentiation and resorption. In addition, Arg-Gly-Asp (RGD)-containing peptides, small molecular inhibitors, and antibodies to αvβ3 integrin have been shown to inhibit bone resorption in vitro and in vivo. Here we examined the effects of a disintegrin HSA-ARLDDL a genetically modified mutant of rhodostomin conjugated with human serum albumin, which is highly selective of αvβ3, on RANKL-induced osteoclastogenesis and ovariectomy (OVX)-induced osteoporosis. In RANKL-induced osteoclastogenesis, HSA-ARLDDL significantly inhibited osteoclast formation, and IC 50 was at nM range. Post-treatment HSA-ARLDDL also inhibits osteoclast formation. Furthermore, weekly administration of HSA-ARLDDL significantly inhibits the increase in serum bone resorption marker levels and decrease in cancellous bone loss in tibia and femur induced by OVX. On the other hand, HSA-ARLDDL did not affect the differentiation and calcium deposition of osteoblasts. These results indicate that the highly selective and long-acting αvβ3 integrin antagonists could be developed as effective drugs for postmenopausal osteoporosis.

原文English
頁(從 - 到)94-101
頁數8
期刊European Journal of Pharmacology
804
DOIs
出版狀態Published - 2017 一月 1

指紋

Osteoclasts
Integrins
Osteoporosis
Bone Resorption
Osteogenesis
Integrin alphaVbeta3
Disintegrins
Postmenopausal Osteoporosis
Osteopontin
Cell Surface Receptors
Ovariectomy
Osteoblasts
Tibia
Serum Albumin
Femur
rhodostomin
Calcium
Bone and Bones
Antibodies
Serum

All Science Journal Classification (ASJC) codes

  • Pharmacology

引用此文

Lin, Tzu Hung ; Yang, Rong Sen ; Tu, Huang Ju ; Liou, Houng Chi ; Lin, Yen Ming ; Chuang, Woei-Jer ; Fu, Wen Mei. / Inhibition of osteoporosis by the αvβ3 integrin antagonist of rhodostomin variants. 於: European Journal of Pharmacology. 2017 ; 卷 804. 頁 94-101.
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abstract = "Integrins are heterodimeric cell surface receptors that mediate cell–cell and cell–matrix interaction. The vitronectin and osteopontin receptor αvβ3 integrin has increased expression levels and is implicated in the adhesion, activation, and migration of osteoclasts on the bone surface as well as osteoclast polarization. αvβ3 integrin plays an important role in osteoclast differentiation and resorption. In addition, Arg-Gly-Asp (RGD)-containing peptides, small molecular inhibitors, and antibodies to αvβ3 integrin have been shown to inhibit bone resorption in vitro and in vivo. Here we examined the effects of a disintegrin HSA-ARLDDL a genetically modified mutant of rhodostomin conjugated with human serum albumin, which is highly selective of αvβ3, on RANKL-induced osteoclastogenesis and ovariectomy (OVX)-induced osteoporosis. In RANKL-induced osteoclastogenesis, HSA-ARLDDL significantly inhibited osteoclast formation, and IC 50 was at nM range. Post-treatment HSA-ARLDDL also inhibits osteoclast formation. Furthermore, weekly administration of HSA-ARLDDL significantly inhibits the increase in serum bone resorption marker levels and decrease in cancellous bone loss in tibia and femur induced by OVX. On the other hand, HSA-ARLDDL did not affect the differentiation and calcium deposition of osteoblasts. These results indicate that the highly selective and long-acting αvβ3 integrin antagonists could be developed as effective drugs for postmenopausal osteoporosis.",
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Inhibition of osteoporosis by the αvβ3 integrin antagonist of rhodostomin variants. / Lin, Tzu Hung; Yang, Rong Sen; Tu, Huang Ju; Liou, Houng Chi; Lin, Yen Ming; Chuang, Woei-Jer; Fu, Wen Mei.

於: European Journal of Pharmacology, 卷 804, 01.01.2017, p. 94-101.

研究成果: Article

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AU - Yang, Rong Sen

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AU - Fu, Wen Mei

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