Adiponectin ameliorates experimental periodontitis in diet-induced obesity mice.

Adiponectin ameliorates experimental periodontitis in diet-induced obesity mice.
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脂联素可改善饮食引起的肥胖小鼠的实验性牙周炎

DOI:
10.1371/journal.pone.0097824
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Chen J
Chen J
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Zhang L;Meng S;Tu Q;Yu L;Tang Y;Dard MM;Kim SH;Valverde P;Zhou X;Chen J

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脂联素是一种脂肪因子,能使身体对胰岛素敏感。据报道,肥胖、糖尿病和牙周炎患者体内脂联素水平较低。在这项研究中,我们建立了雄性脂联素基因敲除和饮食诱导肥胖小鼠的实验性牙周炎,一个肥胖和2型糖尿病的模型,目的是评估脂联素的治疗潜力。我们发现,在两种牙周炎小鼠模型中,系统注射脂联素减少了牙槽骨丢失、破骨细胞活性和炎症细胞的浸润。此外,脂联素治疗降低了实验性牙周炎饮食诱导肥胖小鼠白色脂肪组织中促炎细胞因子的水平。我们的体外研究还发现,叉头盒O1是能量代谢的关键转录调节因子,在破骨细胞脂联素的直接信号传递中发挥着重要作用。因此,脂联素增加了正在分化的破骨细胞前体细胞中叉头盒O1mRNA的表达及其核蛋白水平。抑制c-jun氨基末端激酶信号转导降低叉头盒O1的核蛋白水平。此外,叉头盒O1的过度表达抑制了破骨细胞的生成,并导致激活的T细胞C1核因子的核水平下降。综上所述,这项研究表明,全身应用脂联素可能构成一种潜在的干预疗法,以改善2型糖尿病相关性牙周炎。它还提出,脂联素对破骨细胞生成的抑制涉及叉头盒O1。
Adiponectin is an adipokine that sensitizes the body to insulin. Low levels of adiponectin have been reported in obesity, diabetes and periodontitis. In this study we established experimental periodontitis in male adiponectin knockout and diet-induced obesity mice, a model of obesity and type 2 diabetes, and aimed at evaluating the therapeutic potential of adiponectin. We found that systemic adiponectin infusion reduced alveolar bone loss, osteoclast activity and infiltration of inflammatory cells in both periodontitis mouse models. Furthermore, adiponectin treatment decreased the levels of pro-inflammatory cytokines in white adipose tissue of diet-induced obesity mice with experimental periodontitis. Our in vitro studies also revealed that forkhead box O1, a key transcriptional regulator of energy metabolism, played an important role in the direct signaling of adiponectin in osteoclasts. Thus, adiponectin increased forkhead box O1 mRNA expression and its nuclear protein level in osteoclast-precursor cells undergoing differentiation. Inhibition of c-Jun N-terminal kinase signaling decreased nuclear protein levels of forkhead box O1. Furthermore, over-expression of forkhead box O1 inhibited osteoclastogenesis and led to decreased nuclear levels of nuclear factor of activated T cells c1. Taken together, this study suggests that systemic adiponectin application may constitute a potential intervention therapy to ameliorate type 2 diabetes-associated periodontitis. It also proposes that adiponectin inhibition of osteoclastogenesis involves forkhead box O1.
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