DPP-4 inhibitor impedes lipopolysaccharide-induced osteoclast formation and bone resorption in vivo

Masahiko Ishida, Wei Ren Shen, Keisuke Kimura, Akiko Kishikawa, Kazuhiro Shima, Saika Ogawa, Jiawei Qi, Fumitoshi Ohori, Takahiro Noguchi, Aseel Marahleh, Hideki Kitaura

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)242-253
Number of pages12
JournalBiomedicine and Pharmacotherapy
Publication statusPublished - 2019 Jan


  • Diabetes
  • DPP-4 inhibitor
  • LPS
  • Osteoclast


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