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

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

doi:10.1016/j.biopha.2018.10.052

Cited by 23 publications

(32 citation statements)

References 47 publications

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“…He et al found that M1, but not M2, macrophages were significantly decreased after DPP-4 inhibitor treatments, resulting in a significant decrease in the M1/M2 macrophage ratio [ 44 ]. Similarly, we previously showed that a DPP-4 inhibitor suppressed LPS-induced TNF- α expression in mouse calvaria [ 8 ]. Taking these findings together with the present results, it appears that TNF- α -induced osteoclast formation and root resorption may be inhibited by downregulation of the M1/M2 macrophage ratio in response to linagliptin treatment.…”

Section: Discussionmentioning

confidence: 87%

“…It has recently been identified as an important risk factor for osteoporosis-associated fractures [ 26 , 27 ], but the long-term use of some antidiabetic drugs was reported to have side effects for bone metabolism [ 28 , 29 ]. Indeed, a DPP-4 inhibitor was recently shown to have anti-inflammatory actions in several types of vascular cells and immune cells [ 30 , 31 ], while linagliptin has potent beneficial effects in some inflammatory diseases [ 8 , 32 ]. There are few reports regarding the outcome of short-term DPP-4 inhibitor administration, and this study is the first to report the effect of DPP-4 inhibition on OTM and associated root resorption.…”

Section: Discussionmentioning

confidence: 99%

“…We observed tooth movement of 160.31 ± 9.73 μ m after 12 days; this is similar to that reported in our previous studies, suggesting that the OTM mouse is a reliable animal model. We previously administered 30 μ g (nearly 1.5 mg/kg/day) linagliptin as a DPP-4 inhibitor [ 8 ] to inhibit LPS-induced inflammation in mouse calvaria, so used the same concentration of linagliptin in the present study. OTM in mice is a multifactorial process affected by the type of appliance, magnitude and direction of the force, and type of tooth movement [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

“…Cycling conditions were the following: initial denaturation at 95°C for 30 s, then 50 cycles of 95°C for 5 s, 60°C for 30 s, and a final dissociation stage (95°C for 15 s, 60°C for 30 s, and 95°C for 15 s). Primers were as follows: GAPDH, 5′-GGTGGAGCCAAAAGGGTCA-3′ and 5′-GGGGGCTAAGCAGTTGGT-3′; RANKL, 5′-CCTGAGGCCAGCCATTT-3′ and 5′-CTTGGCCCAGCCTCGAT-3′; TNF- α , 5′-CTGTAGCCCACGTCGTAGC-3′ and 5′-TTGAGATCCATGCCGTTG-3′; OPG, 5′-ATCAGAGCCTCATCACCTT-3′ and 5′-CTTAGGTCCAACTACAGAGGAAC-3′ [ 8 ].…”

Section: Methodsmentioning

confidence: 99%

“…In animal experiments, it was exhibited positive effects on bone metabolism by enhancing bone quality and density, and the expression of bone markers [ 6 ]. Additionally, a DPP-4 inhibitor had a protective effect against tumour necrosis factor (TNF)- α -induced chondrocyte senescence [ 7 ], while we previously showed that a DPP-4 inhibitor inhibited lipopolysaccharide (LPS)-induced osteoclast formation and bone resorption by decreasing LPS-induced TNF- α expression in macrophages [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

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Effect of a DPP-4 Inhibitor on Orthodontic Tooth Movement and Associated Root Resorption

Kitaura

Shen

et al. 2020

BioMed Research International

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Objectives. Dipeptidyl peptidase-4 (DPP-4) inhibitors are used as a treatment for type 2 diabetes mellitus and have also recently been applied to enhance bone quality and density, and increase the expression of bone markers. This study aimed to investigate the effect of a DPP-4 inhibitor on orthodontic tooth movement (OTM) and related root resorption in a mouse model. Materials and Methods. Mice were randomly divided into three groups: those undergoing OTM with the addition of a DPP-4 inhibitor (30 μg), those undergoing OTM and receiving phosphate-buffered saline (PBS), and those without force loading (control group). OTM was achieved by means of a nickel–titanium closed coil spring that moved the first molar in a mesial direction for 12 days. The distance of OTM was measured using silicone impression. Maxillae were removed for histological analysis or real-time PCR analysis. Results. The distance of OTM and the number of osteoclasts were significantly decreased after administration of the DPP-4 inhibitor, which also significantly suppressed the number of odontoclasts and root resorption after OTM. Furthermore, the mRNA expression of tumour necrosis factor-α (TNF-α) and the receptor activator of nuclear factor kappa-B ligand (RANKL) were decreased in DPP-4 inhibitor-treated mice compared with those receiving PBS and control animals. Conclusion. The DPP-4 inhibitor inhibited tooth movement and associated root resorption by blocking the formation of osteoclasts and odontoclasts, respectively. It also appeared to inhibit osteoclastogenesis and odontoclastogenesis by suppressing the expression of TNF-α and/or RANKL.

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effect of a DPP-4 Inhibitor on Orthodontic Tooth Movement and Associated Root Resorption

Kitaura

Shen

et al. 2020

BioMed Research International

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The role of autophagy in SIM mediated anti‐inflammatory osteoclastogenesis through NLRP3 signaling pathway

Cheng,

Jin,

Zheng

et al. 2024

Immunity Inflam & Disease

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BackgroundInflammatory bone resorption is a prominent risk factor for implantation failure. Simvastatin (SIM) has anti‐inflammatory effects independent of cholesterol lowering and reduces osteoclastogenesis by decreasing both the number and activity of osteoclasts. However, the specific mechanism of inflammatory bone loss alleviation by SIM remains to be elucidated. We hypothesized that SIM relieves inflammatory bone loss by modulating autophagy and suppressing the NOD‐like receptor family pyrin domain‐containing protein 3 (NLRP3) signaling pathway.Methods and resultsRAW264.7 cells were stimulated by lipopolysaccharide (LPS) after being pretreated with various concentrations of SIM. Osteoclast (OC) differentiation, formation and activity were evaluated by tartrate‐resistant acid phosphatase staining, F‐actin ring staining and bone resorption pit assays, respectively. We observed autophagosomes by transmission electron microscopy. Then NLRP3 inhibitor MCC950 was used to further explore the corresponding molecular mechanism underlying anti‑inflammatory bone resorption, the expression of autophagy‐related proteins and NLRP3 signaling pathway factors in pre‐OCs were evaluated by western blot analysis, and the expression of OC‑specific molecules was analyzed using reverse transcription‑quantitative polymerase chain reaction. The results showed that SIM decreased the expression of tumor necrosis factor‐α, whereas increased Interleukin‐10. In addition, SIM inhibited LPS‐induced OC differentiation, formation, bone resorption activity, the level of autophagosomes, and OC‑specific markers. Furthermore, SIM significantly suppressed autophagy by downregulating LC3II, Beclin1, ATG7, and NLRP3‐related proteins expression while upregulating P62 under inflammatory conditions.ConclusionsSIM may reduce autophagy secretion to attenuate LPS‐induced osteoclastogenesis and the NLRP3 signaling pathway participates in this process, thus providing theoretical basis for the application of this drug in peri‐implantitis.

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Effects of Incretin Therapy on Skeletal Health in Type 2 Diabetes—A Systematic Review

Viggers,

Rasmussen,

Vestergaard

2023

JBMR Plus

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Diabetes poses a significant risk to bone health, with Type 1 diabetes (T1D) having a more detrimental impact than Type 2 diabetes (T2D). The group of hormones known as incretins, which includes gastric inhibitory peptide (GIP) and glucagon‐like peptide 1 (GLP‐1), play a role in regulating bowel function and insulin secretion during feeding. GLP‐1 receptor agonists (GLP‐1 RAs) are emerging as the primary treatment choice in T2D, particularly when atherosclerotic cardiovascular disease is present. Dipeptidyl peptidase 4 inhibitors (DPP‐4is), although less potent than GLP‐1 RAs, can also be used. Additionally, GLP‐1 RAs, either alone or in combination with GIP, may be employed to address overweight and obesity. Since feeding influences bone turnover, a relationship has been established between incretins and bone health. To explore this relationship, we conducted a systematic literature review following the PRISMA guidelines. While some studies on cells and animals have suggested positive effects of incretins on bone cells, turnover, and bone density, human studies have yielded either no or limited and conflicting results regarding their impact on bone mineral density (BMD) and fracture risk. The effect on fracture risk may vary depending on the choice of comparison drug and the duration of follow‐up, which was often limited in several studies. Nevertheless, GLP‐1 RAs may hold promise for people with T2D who have multiple fracture risk factors and poor metabolic control. Furthermore, a potential new area of interest is the use of GLP‐1 RAs in fracture prevention among overweight and obese people. Based on this systematic review, existing evidence remains insufficient to support a positive or a superior effect on bone health to reduce fracture risk in people with T2D. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

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

Cited by 23 publications

References 47 publications

Effect of a DPP-4 Inhibitor on Orthodontic Tooth Movement and Associated Root Resorption

Effect of a DPP-4 Inhibitor on Orthodontic Tooth Movement and Associated Root Resorption

The role of autophagy in SIM mediated anti‐inflammatory osteoclastogenesis through NLRP3 signaling pathway

Effects of Incretin Therapy on Skeletal Health in Type 2 Diabetes—A Systematic Review

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