摘要
背景:肥胖通常被认为是骨骼强度的正调节因子。随着深入研究,肥胖被认为是骨质疏松症的主要危险因素。一些促炎细胞因子如肿瘤坏死因子-α(TNF-α)和白介素-6(IL-6)是脂肪用于负面调节骨代谢的因素。 目的:本综述旨在总结和批判性地讨论促炎细胞因子治疗肥胖相关性骨病的治疗有效性的令人信服的证据。 结果:肥胖人群和动物血清TNF-α和IL-6水平均高于脂肪组织巨噬细胞产生。这些促炎细胞因子通过自分泌和旁分泌方式调节脂肪细胞的增殖和凋亡,促进脂肪分解,抑制脂质合成和降低血脂。另一方面,TNF-α和IL-6通过内分泌方式调节骨代谢。几个报道表明,TNF-α在分化的某些阶段是成骨细胞的负调节因子,并且正调节破骨细胞增殖和分化。相比之下,IL-6通过复杂的机制影响成骨细胞和破骨细胞,这反映了双重作用。此外,TNF-α和IL-6可通过调节从脂肪细胞释放的脂联素和瘦蛋白间接调节骨代谢。 结论:本文首先总结了TNF-α和IL-6在脂质和骨代谢中的作用。我们进一步讨论TNF-α和IL-6如何调节脂肪和骨骼之间的交流及其在肥胖相关骨骼疾病中的病理作用。最后,我们讨论使用促炎症信号通路作为开发肥胖相关性骨病的药物的治疗靶点的可能性。
关键词: TNF-α,IL-6,骨代谢,脂质代谢,肥胖,骨质疏松。
图形摘要
Current Drug Targets
Title:Pro-Inflammatory Cytokines: New Potential Therapeutic Targets for Obesity-Related Bone Disorders
Volume: 18 Issue: 14
关键词: TNF-α,IL-6,骨代谢,脂质代谢,肥胖,骨质疏松。
摘要: Background: Obesity was traditionally considered as a positive regulator on the strength of bone. With the in-depth study, obesity is considered as a major risk factor for osteoporosis. Some proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) are the factors that fat uses to negatively regulate bone metabolism.
Objective: This review was aimed to summarize and critically discuss the convincing evidence for the therapeutic effectiveness of pro-inflammatory cytokines for the treatment of obesity-related bone disorders.
Results: Obese people and animals show a higher level of serum TNF-α and IL-6, which are produced by macrophages derived from adipose tissue. These pro-inflammatory cytokines regulate the proliferation and apoptosis of adipocyte, promote lipolysis, inhibit lipid synthesis and decrease blood lipids through autocrine and paracrine way. On the other hand, TNF-α and IL-6 regulate bone metabolism through the endocrine way. Several reports suggest that TNF-α is a negative regulator of osteoblast at some stages of differentiation and positively regulates osteoclast proliferation and differentiation. In contrast, IL-6 influences osteoblasts and osteoclasts through complex mechanisms, which reflect dual effects. In addition, TNF-α and IL-6 may regulate bone metabolism indirectly by regulating adiponectin and leptin released from adipocytes.
Conclusion: In this review, we first summarize the role of TNF-α and IL-6 in lipid and bone metabolisms. We further discuss how TNF-α and IL-6 regulate the communication between fat and bone, and their pathological roles in obesity-related bone disorders. Lastly, we discuss the possibility of using pro-inflammatory signaling pathway as a therapeutic target to develop drug for obesity-related bone disorders.
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Cite this article as:
Pro-Inflammatory Cytokines: New Potential Therapeutic Targets for Obesity-Related Bone Disorders, Current Drug Targets 2017; 18 (14) . https://dx.doi.org/10.2174/1389450118666170104153512
DOI https://dx.doi.org/10.2174/1389450118666170104153512 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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