The Glucagon-Like Peptide-1 Receptor Agonist Exendin-4 Inhibits Lipopolysaccharide-Induced Osteoclast Formation and Bone Resorption via Inhibition of TNF-α Expression in Macrophages. (13th March 2018)

• Record Type: Journal Article
• Authors: Shen, Wei-Ren; Kimura, Keisuke; Ishida, Masahiko; Sugisawa, Haruki; Kishikawa, Akiko; Shima, Kazuhiro; Ogawa, Saika; Qi, Jiawei; Kitaura, Hideki
• Other Names: Liu Hao Academic Editor.
• Is Part Of: Journal of immunology research. Volume 2018(2018)
• Publication Date: 2018-03-13
• Subjects: Immunology -- Periodicals; Immunology -- Research -- Periodicals; 616.07905
• DOI: 10.1155/2018/5783639
• Languages: English
• ISSNs: 2314-8861

Abstract

Abstract : Glucagon-like peptide-1 (GLP-1) receptor agonists are an effective treatment approach for type 2 diabetes. Recently, anti-inflammatory effects of GLP-1 receptor agonists have also been reported. Lipopolysaccharide (LPS) induces inflammation and osteoclast formation. In this study, we investigated the effect of exendin-4, a widely used GLP-1 receptor agonist, in LPS-induced osteoclast formation and bone resorption. LPS with or without exendin-4 was administered on mouse calvariae by daily subcutaneous injection. The number of osteoclasts, the ratio of bone resorption pits, and the level of C-terminal cross-linked telopeptide of type I collagen (CTX) were significantly lower in LPS- and exendin-4-coadministered mice than in mice administered with LPS alone. RANKL and TNF- α mRNA expression levels were lower in the exendin-4- and LPS-coadministered group than in the LPS-administered group. Our in vitro results showed no direct effects of exendin-4 on RANKL-induced osteoclast formation, TNF- α -induced osteoclast formation, or LPS-induced RANKL expression in stromal cells. Conversely, TNF- α mRNA expression was inhibited in the exendin-4- and LPS-cotreated macrophages compared with cells treated with LPS alone. These results indicate that the GLP-1 receptor agonist exendin-4 may inhibit LPS-induced osteoclast formation and bone resorption by inhibiting LPS-induced TNF- α production in macrophages.