DPP-4 inhibitor impedes lipopolysaccharide-induced osteoclast formation and bone resorption in vivo - 09/12/18
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Highlights |
• | DPP-4 inhibitor inhibited LPS-induced osteoclast formation and bone resorption. |
• | DPP-4 inhibitor inhibited LPS-induced osteoclast-related cytokines in vivo. |
• | DPP-4 inhibitor downregulated LPS-induced TNF-α production by macrophages in vivo. |
• | DPP-4 inhibitor did not directly affect osteoclast formation. |
Abstract |
Objectives |
Dipeptidyl peptidase 4 (DPP-4) inhibition is a new therapeutic strategy for type 2 diabetic patients. DPP-4 has been reported to enhance inflammation. However, the effect of DPP-4 inhibition on inflammation remains unknown. Lipopolysaccharide (LPS) is a strong inducer of inflammation and osteoclast formation. In this study, we investigated in vivo effects of DPP-4 inhibition on LPS-induced osteoclast formation and bone resorption, as well as in vitro effects of DPP-4 inhibition on RANKL-induced osteoclastogenesis and TNF-α-induced osteoclastogenesis.
Methods |
LPS with or without a DPP-4 inhibitor was subcutaneously injected into mouse calvaria for 5 days. Histological sections of calvaria were stained for tartrate-resistant acid phosphatase, and osteoclast numbers were determined. The ratio of calvaria bone resorption was evaluated via microfocal computed tomography reconstruction images.
Results |
Osteoclast number and bone resorption were significantly lower in mice that underwent LPS and DPP-4 inhibitor co-administration than in those that underwent LPS administration alone. Moreover, RANKL, TNF-α, and M-CSF expression was reduced in the LPS and DPP-4 inhibitor co-administration group. In vitro, there were no direct effects of DPP-4 inhibitor or DPP-4 on RANKL- and TNF-α-induced osteoclastogenesis, or on LPS-induced RANKL expression in stromal cells. Nevertheless, macrophages from LPS and DPP-4 inhibitor co-administered mice exhibited lower TNF-α expression than macrophages from LPS-only mice. Notably, TNF-α expression was not reduced in LPS and DPP-4 inhibitor co-treated macrophages in vitro, compared with macrophages treated with LPS alone.
Le texte complet de cet article est disponible en PDF.Abbreviations : ANOVA, DPP-4, EDTA, FBS, GAPDH, LPS, M-CSF, PBS, RANKL, TRAP, TNF, CTX
Keywords : Osteoclast, DPP-4 inhibitor, LPS, Diabetes
Plan
Vol 109
P. 242-253 - janvier 2019 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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