Abstract:
Osteoclasts are large, multinucleated cells that are responsible for the resorption of
bone. Bone degenerative diseases, such as osteoporosis, are characterized by overactive osteoclasts.
Receptor activator of nuclear factor- B (NF- B) ligand (RANKL) binding to its receptor on osteoclast
precursors will trigger osteoclast formation and resorption. The production of reactive oxygen
species (ROS) is known to play a crucial role in RANKL-induced osteoclast formation and resorption.
G-protein coupled receptor 120 (GPR120) signalling has been shown to affect osteoclast formation,
but the exact mechanisms of action require further investigation. RAW264.7 murine macrophages
were seeded into culture plates and exposed to the GPR120 agonist, TUG-891, at varying concentrations
(20–100 M) and RANKL to induce osteoclast formation. TUG-891 was shown to inhibit
osteoclast formation and resorption without affecting cell viability in RAW264.7 macrophages. TUG-
891 further decreased ROS production when compared to RANKL only cells. Antioxidant proteins,
Nrf2, HO-1 and NQO1 were shown to be upregulated while the ROS inducing protein, Nox1,
was downregulated by TUG-891. Gene silencing revealed that TUG-891 exerted its effects specifically
through GPR120. This study reveals that GPR120 signalling may inhibit osteoclast formation and
resorption through inhibition on ROS production.
