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.