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

الملخص EN

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.