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Myristoleic acid inhibits osteoclast formation and bone resorption by suppressing the RANKL activation of Src andPyk2

Cited 11 time in Web of Science Cited 11 time in Scopus
Authors
Kwon, Jun-Oh; Jin, Won Jong; Kim, Bongjun; Kim, Hong-Hee; Lee, Zang Hee
Issue Date
2015-12
Publisher
Elsevier
Citation
European Journal of Pharmacology, vol.768, pp. 189–198
Keywords
Myristoleic acidOsteoclastMyristoylationSrcPyk2
Abstract
Cytoskeletal changes in osteoclasts such as formation of actin ring is required for bone-resorbing activity.
The tyrosine kinase Src is a key player in massive cytoskeletal change of osteoclasts, thereby in bone
destruction. In order for Src to be activated, trafficking to the inner plasma membrane via myristoylation
is of importance. A previous study reported that myristoleic acid derived from myristic acid, inhibited
N-myristoyl-transferase, an essential enzyme for myristoylation process. This prompted us to investigate
whether myristoleic acid could affect osteoclastogenesis. Indeed, we observed that myristoleic acid inhibited
RANKL-induced osteoclast formation in vitro, especially, at later stages of differentiation. Myristoleic
acid attenuated the tyrosine phosphorylation of c-Src and Pyk2, which associates with Src, by
RANKL. When myristoleic acid was co-administered with soluble RANKL into mice, RANKL-induced bone
loss was substantially prevented. Bone dissection clearly revealed that the number of multinucleated
osteoclasts was significantly diminished by myristoleic acid. On the other hand, myristoleic acid treatment
had little or no influence on early osteoclast differentiation markers, such as c-Fos and NFATc1, and
proteins related to cytoskeletal rearrangement, including DC-STAMP, integrin αv and integrin β3 in vitro.
Taken together, our data suggest that myristoleic acid is capable of blocking the formation of large
multinucleated osteoclasts and bone resorption likely through suppressing activation of Src and Pyk2.
Language
English
URI
https://hdl.handle.net/10371/95801
DOI
https://doi.org/10.1016/j.ejphar.2015.10.053
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College of Dentistry/School of Dentistry (치과대학/치의학대학원)Dept. of Dentistry (치의학과)Journal Papers (저널논문_치의학과)
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