The Glucagon-Like Peptide-1 Receptor Agonist Exendin-4 Inhibits Lipopolysaccharide-Induced Osteoclast Formation and Bone Resorption via Inhibition of TNF-<i>α</i>Expression in Macrophages

Shen, Wei; Kimura, Keisuke; Ishida, Masahiko; Sugisawa, Haruki; Kishikawa, Akiko; Shima, Kazuhiro; Ogawa, Saika; Qi, Jiawei; Kitaura, Hideki

doi:10.1155/2018/5783639

Cited by 28 publications

(36 citation statements)

References 47 publications

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“…22,24 A direct effect of exendin-4, via GLP-1 receptors on osteoclasts, may not be possible because minimal in vitro effects have been observed. 14,22 Subcutaneous injections of exendin-4 increased bone formation markers and in vivo osteoblast number of ovariectomized rats. 20 Additionally, exendin-4 promoted differentiation of bone marrow stromal cells into osteoblasts by synergizing with the Wnt signaling pathway.…”

Section: Discussionmentioning

confidence: 98%

“…24,25 Exendin-4 improves diabetes-induced, ovariectomyinduced, and high fat diet-induced osteoporosis in rodent models. [18][19][20]22,26,27 Underlying mechanisms may include reduction of the RANKL/OPG ratio [18][19][20] and TNF-a expression level 14 in bone tissue, as well as reduction of serum calcitonin level. 22,24 A direct effect of exendin-4, via GLP-1 receptors on osteoclasts, may not be possible because minimal in vitro effects have been observed.…”

Section: Discussionmentioning

confidence: 99%

“…Receptor activator of nuclear factor kappa-B ligand (RANKL) 9,10 and TNF-a 11,12 are crucial for differentiation of osteoclasts and odontoclasts during orthodontic tooth movement. Exendin-4 can inhibit TNF-a expression 13,14 and TNF-a-induced inflammation or reactions. [15][16][17] Increased levels of RANKL expression in the bone of osteoporotic rodents have been ameliorated by administration of exendin-4.…”

Section: Introductionmentioning

confidence: 99%

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Local administration of high-dose diabetes medicine exendin-4 inhibits orthodontic tooth movement in mice

Shen¹,

Kitaura²,

Qi³

et al. 2020

The Angle Orthodontist

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Objectives To investigate the effects of exendin-4 on orthodontic tooth movement distance, root resorption, and expression levels of osteoclast-related cytokines in a mouse model. Materials and Methods A 10-g NiTi coil spring was placed between the anterior alveolar bone and upper left first molar of 8-week-old male C57BL/6 mice. Twenty microliters of exendin-4 solution (containing 0.2 μg, 4 μg, or 20 μg exendin-4) or phosphate-buffered saline (PBS) were injected on the buccal side of the upper left first molar at 2-day intervals (4 mice per group). Mice were sacrificed on day 12; silicone impressions were taken to record tooth movement distance. The left maxillae of the PBS and 20 μg exendin-4 groups were also excised for histological analysis and quantitative reverse transcription polymerase chain reaction analysis. Results Orthodontic tooth movement distance was smaller in the 20 μg exendin-4 group than in the PBS group (P < .01). Compared with the PBS group, the 20 μg exendin-4 group showed lower osteoclast number (P < .05), odontoclast number (P < .05), and root resorption surface percentage (P < .05). Relative to maxillae with PBS injections, maxillae with 20 μg exendin-4 injections had lower receptor activator of nuclear factor kappa-B ligand (RANKL) mRNA expression (P < .05), TNF-α mRNA expression (P < .05), and RANKL/osteoprotegerin (OPG) ratio (P<.01). There were no differences in the expression of OPG mRNA. Conclusions Exendin-4 inhibits orthodontic tooth movement. Therefore, additional attention is needed for orthodontic patients who receive exendin-4 for diabetes treatment. GLP-1 receptor may be a treatment target for patients with severe root resorption.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Local administration of high-dose diabetes medicine exendin-4 inhibits orthodontic tooth movement in mice

Shen¹,

Kitaura²,

Qi³

et al. 2020

The Angle Orthodontist

Self Cite

View full text Add to dashboard Cite

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“…The cells were incubated for 2 h at 37 °C. The absorbance at 450 nm was then measured for each well with a microplate reader (Remote Sunrise; Tecan, Japan) as previously reported [ 42 ].…”

Section: Methodsmentioning

confidence: 99%

Anti-c-fms Antibody Prevents Osteoclast Formation and Bone Resorption in Co-Culture of Osteoblasts and Osteoclast Precursors In Vitro and in Ovariectomized Mice

Nara

Kitaura

Ogawa

et al. 2020

IJMS

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Osteoporosis morphology is characterized by bone resorption and decreases in micro-architecture parameters. Anti-osteoporosis therapy targets osteoclasts because bone resorption is a unique function of osteoclasts. Anti-c-fms antibodies against the receptor for macrophage colony-stimulating factor (M-CSF) inhibit osteoclast formation and bone resorption in vitro and in vivo. However, the effect of anti-c-fms antibodies on bone resorption in ovariectomized (OVX) mice is unknown. In this study, we evaluated the effect of anti-c-fms antibodies on osteoclast formation and bone resorption in osteoblast–osteoclast precursor co-culture in vitro and in OVX mice. Osteoblast and osteoclast precursor co-cultures treated with anti-c-fms antibodies showed significantly inhibited osteoclast formation, while cultures without anti-c-fms antibody treatment showed osteoclast formation. However, anti-c-fms antibodies did not change the receptor activator of nuclear factor kappa-B ligand (RANKL) or osteoprotegrin (OPG) expression during osteoblast and osteoclast differentiation in vitro. These results indicate that anti-c-fms antibodies directly affected osteoclast formation from osteoclast precursors in co-culture. OVX mice were treated with intraperitoneal injections of anti-c-fms antibody. The trabecular bone structure of the femur was assessed by micro-computer tomography. The anti-c-fms antibody inhibited osteoclast formation and bone loss compared with PBS-treated OVX mice. These results indicate potential for the therapeutic application of anti-c-fms antibodies for postmenopausal osteoporosis.

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“…Shaded areas of the same color density were considered bone destruction areas. The ratio of bone resorption area to total area was measured using ImageJ (NIH, Bethesda, MD, USA) [34].…”

Section: Micro-ct Analysis For Bone Destructionmentioning

confidence: 99%

IL-33 Inhibits TNF-α-Induced Osteoclastogenesis and Bone Resorption

Ohori

Kitaura

Ogawa

et al. 2020

IJMS

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Interleukin (IL)-33 is a member of the IL-1 family, which acts as an alarmin. Several studies suggested that IL-33 inhibited osteoclastogenesis and bone resorption. Tumor necrosis factor-α (TNF-α) is considered a direct inducer of osteoclastogenesis. However, there has been no report regarding the effect of IL-33 on TNF-α-induced osteoclastogenesis and bone resorption. The objective of this study is to investigate the role of IL-33 on TNF-α-induced osteoclastogenesis and bone resorption. In an in vitro analysis of osteoclastogenesis, osteoclast precursors, which were derived from bone marrow cells, were treated with or without IL-33 in the presence of TNF-α. Tartrate-resistant acid phosphatase (TRAP) staining solution was used to assess osteoclast formation. In an in vivo analysis of mouse calvariae, TNF-α with or without IL-33 was subcutaneously administrated into the supracalvarial region of mice daily for 5 days. Histological sections were stained for TRAP, and osteoclast numbers were determined. Using micro-CT reconstruction images, the ratio of bone destruction area on the calvariae was evaluated. The number of TRAP-positive cells induced by TNF-α was significantly decreased with IL-33 in vitro and in vivo. Bone resorption was also reduced. IL-33 inhibited IκB phosphorylation and NF-κB nuclear translocation. These results suggest that IL-33 inhibited TNF-α-induced osteoclastogenesis and bone resorption.

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The Glucagon-Like Peptide-1 Receptor Agonist Exendin-4 Inhibits Lipopolysaccharide-Induced Osteoclast Formation and Bone Resorption via Inhibition of TNF-αExpression in Macrophages

Cited by 28 publications

References 47 publications

Local administration of high-dose diabetes medicine exendin-4 inhibits orthodontic tooth movement in mice

Local administration of high-dose diabetes medicine exendin-4 inhibits orthodontic tooth movement in mice

Anti-c-fms Antibody Prevents Osteoclast Formation and Bone Resorption in Co-Culture of Osteoblasts and Osteoclast Precursors In Vitro and in Ovariectomized Mice

IL-33 Inhibits TNF-α-Induced Osteoclastogenesis and Bone Resorption

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