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.
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.
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DOI：
10.1155/2018/5783639
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发表时间：
2018
影响因子：
4.1
通讯作者：
Kitaura H
中科院分区：
文献类型：
--
作者：
Shen WR;Kimura K;Ishida M;Sugisawa H;Kishikawa A;Shima K;Ogawa S;Qi J;Kitaura H
胰高血糖素样肽-1（GLP-1）受体激动剂是2型糖尿病的有效治疗方法。最近，还报道了GLP-1受体激动剂的抗炎作用。脂多糖（LPS）诱导炎症和破骨细胞形成。在这项研究中，我们研究了广泛使用的GLP-1受体激动剂exendin-4在LPS诱导的破骨细胞形成和骨吸收中的作用。通过每日皮下注射在小鼠颅骨上施用具有或不具有毒蜥外泌肽-4的LPS。破骨细胞的数量，骨吸收坑的比例，和C-末端交联的端肽的I型胶原蛋白（CTX）的水平显着低于LPS和exendin-4-co-administered小鼠比单独使用LPS。Exendin-4和LPS联合给药组的RANKL和TNF-α mRNA表达水平低于LPS给药组。我们的体外结果显示exendin-4对基质细胞中RANKL诱导的破骨细胞形成、TNF-α诱导的破骨细胞形成或LPS诱导的RANKL表达无直接影响。相反，与单独LPS处理的细胞相比，Exendin-4和LPS共同处理的巨噬细胞中TNF-α mRNA表达受到抑制。这些结果表明，GLP-1受体激动剂exendin-4可能通过抑制LPS诱导的巨噬细胞中TNF-α的产生来抑制LPS诱导的破骨细胞形成和骨吸收。
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.
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影响因子：
2.8
作者：
Moayeri A;Mohamadpour M;Mousavi SF;Shirzadpour E;Mohamadpour S;Amraei M
通讯作者：
Amraei M
影响因子：
4.5
作者：
Mabilleau, Guillaume;Mieczkowska, Aleksandra;Chappard, Daniel
通讯作者：
Chappard, Daniel
影响因子：
4.4
作者：
Kitaura, H;Sands, MS;Teitelbaum, SL
通讯作者：
Teitelbaum, SL
影响因子：
4.2
作者：
Bazelier, Marloes T.;Vestergaard, Peter;de Vries, Frank
通讯作者：
de Vries, Frank
影响因子：
3.5
作者：
Chung, Y. -H.;Chang, E. -J.;Ko, J. S.
通讯作者：
Ko, J. S.