ROLE OF CYTOKINES IN BONE-RESORPTION
ROLE OF CYTOKINES IN BONE-RESORPTION
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DOI：
10.1016/8756-3282(95)00180-l
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发表时间：
1995-08-01
期刊：
影响因子：
4.1
通讯作者：
MANOLAGAS, SC
中科院分区：
文献类型：
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作者：
MANOLAGAS, SC
近年来已证实，白介素1、6、11和肿瘤坏死因子可刺激破骨细胞的发育，从而促进骨吸收的过程，此外，白介素6的产生和/或作用的上调与以过度破骨细胞性骨吸收为特征的疾病状态的发病有关，包括与卵巢或睾丸功能丧失相关的骨量减少。本文着重介绍了这一证据，并试图阐明细胞因子在性腺功能缺乏引起的骨丢失中的作用。综述了雌激素和雄激素对骨骼的保护作用是通过它们抑制IL-6产生的能力来实现的，这两种类固醇都是通过涉及各自特定受体的机制来抑制IL-6基因启动子的转录活性来发挥作用的，当两性失去性腺功能时，都会出现由IL-6介导的破骨细胞形成上调，与此一致，IL-6缺陷小鼠在卵巢或切除后不会表现出破骨细胞的增加，并受到保护，不受两性性腺功能丧失所导致的骨丢失的影响。尽管这些观察证实IL-6是性腺功能缺乏引起的骨丢失的重要致病因素，但目前尚不清楚IL-6是唯一的致病因素还是IL-1、肿瘤坏死因子和IL-11也可能参与其中，然而，与IL-6相反，这些细胞因子似乎不受性激素的直接调节，因此，它们不太可能是该病的致病因素；然而，由于它们是破骨细胞发育所必需的，它们可能是性腺功能缺乏导致骨丢失的参与性因素。
It has been established during the past few years that interleukin(s)-1, -6, -11 (IL-I, IL-6, IL-11), and tumor necrosis factor (TNF) can stimulate osteoclast development and thereby the process of bone resorption, Moreover, upregulation of the production and/or action of IL-6 has been implicated in the pathogenesis of disease states characterized by excessive osteoclastic bone resorption, including the osteopenias associated with loss of either ovarian or testicular function, This article highlights this evidence and attempts to clarify the role of cytokines in the bone loss associated with gonadal deficiency, Specifically, it reviews data demonstrating that the protective effects of estrogens and androgens on the skeleton are mediated through their ability to inhibit IL-6 production, Both of these steroids exert their effects by inhibiting the transcriptional activity of the IL-6 gene promoter via mechanisms involving their respective specific receptors, Upon loss of gonadal function in either sex, there occurs an upregulation of osteoclast formation which is mediated by IL-6, Consistent with this, IL-6 deficient mice do not exhibit an increase in the formation of osteoclasts after ovariectomy or orchidectomy, and are protected from the bone loss caused by the loss of gonadal function in either sex, Even though these observations establish that IL-6 is an essential pathogenetic factor in the bone loss caused by gonadal deficiency, it remains unclear whether IL-6 is the sole pathogenetic factor or whether IL-1, TNF, and IL-11 may also be involved, However, in contrast to IL-6, these cytokines do not seem to be directly regulated by sex steroids, Therefore, it is unlikely that they are causative factors in the pathogenesis of this condition; yet, because they are required for osteoclast development, they may be participatory factors in the bone loss caused by gonadal deficiency.