ECTS Abstracts (2015) 1 P199

Myristoleic Acid Inhibits Formation of Multinucleated Osteoclasts and Bone Resorption Activity by Suppressing Activation of Src and Pyk2

Jun-Oh Kwon, Hong-Hee Kim & Zang Hee Lee

Seoul National University School of Dentistry, Seoul, Republic of Korea.

Cytoskeletal changes in osteoclasts (OC) such as formation of actin ring or focal adhesion are an essential process leading to bone destruction. Therefore, some kinases involved in this process involving Src, integrin-linked kinase (ILK), or focal adhesion kinase (Pyk) may play a pivotal role in massive cytoskeletal change of OC, thereby destructing bone. It has been well appreciated that in order to for these kinases to be working on membrane anchoring of these kinases via myristoylation or phosphorylation is of importance. Myristoleic acid is an omega-5 fatty acid obtained from the plant seeds of the Myristicaceae, or biosnynthesised from myristic acid by the delta-9 desaturase. We observed that myristoleic acid inhibited RANKL-induced osteoclast formation, especially, at later stages and significantly attenuated phosphorylation of c-Src or Pyk in vitro. When myristoleic acid was co-administered with soluble RANKL into mice substantial degree of bone loss was prevented by myristoleic acid. Bone dissection clearly revealed that TRAP+ OC were significantly diminished with the treatment of myrostoleic acid. On the other hand, myristoleic acid treatment per se neither did block nor induce a number of common OC differentiation or maturation markers including c-Fos, NFATc1, DC-STAMP, integrin αv and integrin β3 in vitro. ALP assay suggested that myristoleic acid did not give rise to an osteogenic potential. Interestingly, myristoleic acid substantially blocked bone resorption. Taken together, our data suggest that myristoleic acid is capable of blocking formation of multinucleated OC and bone resorption likely through suppressing activation of Src and Pyk2.

Disclosure: The authors declared no competing interests.

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