A bone-protective role for IL-17 receptor signaling in ovariectomy-induced bone loss.
A bone-protective role for IL-17 receptor signaling in ovariectomy-induced bone loss.
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DOI：
10.1002/eji.200939670
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发表时间：
2009-10
影响因子：
5.4
通讯作者：
Gaffen, Sarah L.
中科院分区：
文献类型：
--
作者：
Goswami, Jaya;Hernandez-Santos, Nydiaris;Zuniga, Luis A.;Gaffen, Sarah L.
绝经后骨质疏松症被认为是一个炎症过程，在这个过程中，许多促炎细胞因子和T细胞衍生的细胞因子发挥了破坏骨质的作用。IL-17A是促炎性Th17细胞的标志性细胞因子，在影响骨转换的疾病中扮演着两种角色。虽然IL-17A在类风湿性关节炎中促进骨丢失，但在牙周病模型中它对病原体诱导的骨破坏具有保护作用。我们利用IL-17RAKO小鼠去卵巢诱导的骨质疏松症(OVX)模型来评价IL-17A在雌激素缺乏引起的骨丢失中的作用。出乎意料的是，IL-17RAKO小鼠始终比对照组更容易受到OVX诱导的骨丢失的影响。血清中典型的Th1、Th2或Th17细胞因子没有变化，这可能是骨丢失增加的原因。然而，IL-17RAKO小鼠表现出结构性的瘦素升高，去势后瘦素进一步增加。IL-17A和IL-17F处理3T3-L1前脂肪细胞始终抑制脂肪生成，导致瘦素的产生减少。除了调节新陈代谢和饱腹感之外，瘦素还可以调节骨代谢。因此，这些数据表明，IL-17A负性调节脂肪生成和随后的瘦素表达，这与去卵巢期间骨破坏增加有关。
Post-menopausal osteoporosis is considered to be an inflammatory process, in which numerous pro-inflammatory and T cell-derived cytokines play a bone-destructive role. IL-17A is the signature cytokine of the pro-inflammatory Th17 population, and plays dichotomous roles in diseases that affect bone turnover. Whereas IL-17A promotes bone loss in rheumatoid arthritis, it is protective against pathogen-induced bone destruction in a periodontal disease model. We used a model of ovariectomy-induced osteoporosis (OVX) in IL-17RAKO mice to evaluate the role of the IL-17A in bone loss caused by estrogen deficiency. Unexpectedly, IL-17RAKO mice were consistently and markedly more susceptible to OVX-induced bone loss than controls. There were no changes in prototypical Th1, Th2 or Th17 cytokines in serum that could account for increased bone loss. However, IL-17RAKO mice exhibited constitutively elevated leptin, which further increased following OVX. Consistently, IL-17A and IL-17F treatment of 3T3-L1 pre-adipocytes inhibited adipogenesis, leading to reduced production of leptin. In addition to its role in regulating metabolism and satiety, leptin can regulate bone turnover. Accordingly, these data show that IL-17A negatively regulates adipogenesis and subsequent leptin expression, which correlates with increased bone destruction during OVX.
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影响因子：
4.1
作者：
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通讯作者：
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