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-κB (NF-κB) 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 µM) 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.

Highlights

  • The skeleton is a metabolically active and dynamic tissue which allows for the movement of muscles and protection and support of vital organs [1]

  • Numerous studies have reported on the bone protective effects of ω-3 LCPUFAs [16,17,18,19]

  • This has led to an interest in understanding the role of G-protein coupled receptor 120 (GPR120) in mediating the effects of ω-3 LCPUFAs in bone

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Summary

Introduction

The skeleton is a metabolically active and dynamic tissue which allows for the movement of muscles and protection and support of vital organs [1]. Bone is continuously repaired by a process known as bone remodelling, whereby osteoclasts resorb old bone and osteoblasts form new bone, to maintain the strength and integrity of bone [2]. Osteoclasts are large multinucleated bone cells that are derived from the monocyte-macrophage lineage of haematopoietic stem cells [3]. Osteoclasts are capable of resorbing bone when stimulated by receptor activator of nuclear factor-κB ligand (RANKL) binding to its receptor, RANK, on osteoclast precursors [1]. Over-active osteoclasts can lead to bone degenerative disorders such as osteoporosis. Targeting osteoclast formation represents a viable strategy in the treatment of such bone degenerative disorders

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