Abstract：
:Excessive osteoclast leads to the imbalance in bone reconstruction and results in osteolytic diseases, such as osteoporosis and rheumatic arthritis. Integrin αvβ3 abundantly expresses on osteoclast and plays a critical role in the formation and function of osteoclast, therefore, blockage of αvβ3 has become an attractive therapeutic option for osteolytic diseases. In this study, we find that Tablysin-15, a RGD motif containing disintegrin, concentration-dependently suppresses RANKL-induced osteoclastogenesis, F-actin ring formation and bone resorption without affecting the cell viabilities. Tablysin-15 binds to integrin αvβ3 and inhibits the activation of FAK-associated signaling pathways. Tablysin-15 also suppresses the activation of NF-кB, MAPK, and Akt-NFATc1 signaling pathways, which are crucial transcription factors during osteoclast differentiation. Moreover, Tablysin-15 decreases the osteoclastogenesis marker gene expression, including MMP-9, TRAP, CTSK, and c-Src. Finally, Tablysin-15 significantly inhibits LPS-induced bone loss in a mouse model. Taken together, our results indicate that Tablysin-15 significantly suppresses osteoclastogenesis in vitro and in vivo, thus it might be a excellent candidate for treating osteolytic-related diseases.
journal_name
Chem Biol Interactjournal_title
Chemico-biological interactionsauthors
Zeng Q,Lu W,Deng Z,Wu J,Guo R,Xu Xdoi
10.1016/j.cbi.2020.109179subject
Has Abstractpub_date
2020-08-25 00:00:00pages
109179eissn
0009-2797issn
1872-7786pii
S0009-2797(20)30653-0journal_volume
327pub_type
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journal_title：Chemico-biological interactions
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更新日期：2013-01-25 00:00:00
