Adiponectin inhibits osteoclast formation stimulated by lipopolysaccharide from Actinobacillus actinomycetemcomitans.
Adiponectin inhibits osteoclast formation stimulated by lipopolysaccharide from Actinobacillus actinomycetemcomitans.
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DOI：
10.1111/j.1574-695x.2006.00164.x
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发表时间：
2007-02
影响因子：
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通讯作者：
N. Yamaguchi;T. Kukita;Yin-Ji Li;Jose Guillermo Martinez Argueta;Toshiyuki Saito;S. Hanazawa;Y. Yamashita
中科院分区：
文献类型：
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作者：
N. Yamaguchi;T. Kukita;Yin-Ji Li;Jose Guillermo Martinez Argueta;Toshiyuki Saito;S. Hanazawa;Y. Yamashita
以往的流行病学研究表明，牙周病与肥胖和糖耐量密切相关。鉴于肥胖和2型糖尿病患者血浆中脂肪细胞来源的细胞因子脂联素水平降低的报道，我们利用高效破骨细胞形成克隆RAW264的D克隆来探讨脂联素在牙周炎发病机制中的作用，以确定脂联素是否在牙周病细菌脂多糖刺激的破骨细胞形成中起调节作用。我们观察到脂联素对Toll样受体4(TLR4)配体和核因子-kappaB受体激活剂(RANKL)刺激的破骨细胞形成有明显的抑制作用。由于核因子-kappaB是破骨细胞形成过程中的重要转录因子，我们研究了脂联素对其转录活性的影响。荧光素酶分析表明，脂联素能够抑制RAW264细胞中TLR4介导的NF-kappaB活性。此外，我们观察到细胞因子实际上能够抑制TLR4介导的诱导型一氧化氮合酶基因的表达和细胞内一氧化氮的产生。这些观察结果有力地表明，脂联素在牙周病中可能是脂多糖/RANKL介导的破骨细胞形成的负调节因子。
Previous epidemiologic studies have suggested that periodontal disease is closely related to obesity and glucose tolerance. As the level of adiponectin, an adipocyte-derived cytokine, in plasma had been reported to decrease in obese and type 2 diabetes patients, we explored the role of adiponectin in the etiology of periodontitis using the D clone of RAW264, a clone that exhibits highly efficient osteoclast formation, to determine whether adiponectin acts as a regulatory molecule in osteoclast formation stimulated by lipopolysaccharide of periodontopathic bacteria. We observed that adiponectin acted as a potent inhibitor of osteoclast formation stimulated by Toll-like receptor 4 (TLR4) ligand and receptor activator of NF-kappaB ligand (RANKL). Because NF-kappaB is an important transcription factor in osteoclast formation, we examined the effect of adiponectin on its transcriptional activity. A luciferase assay showed that adiponectin was able to inhibit the TLR4-mediated NF-kappaB activity in RAW264 cells. In addition, we observed that the cytokine was actually able to inhibit TLR4-mediated expression of the gene for inducible nitric oxide synthase and production of nitric oxide in the cells. These observations strongly suggest that adiponectin may function as a negative regulator of lipopolysaccharide/RANKL-mediated osteoclast formation in periodontal disease.