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| 2,3,7,8-四氯二苯并对二噁英对骨代谢的影响及机制的研究进展 |
| The effect and mechanism of 2,3,7,8-tetrachlorodibenzo-p-dioxin on bone metabolism |
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| DOI：10.3969/j.issn.1006.7108.2019.07.032 |
| 中文关键词: 2,3,7,8-四氯二苯并对二噁英 芳香烃受体 骨代谢 骨重建 抗雌激素效应 |
| 英文关键词:2,3,7,8-tetra-chlorodibenzo-p-dioxin aryl hydrocarbon receptor bone metabolism bone remodeling anti-estrogen effect |
| 基金项目:中国医科大学大学生创新创业训练计划资助项目(201810159113) |
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| 中文摘要: |
| 2,3,7,8-四氯二苯并对二噁英（2,3,7,8-tetrachlorodibenzo-p-dioxin，TCDD）是一类毒性极强的二噁英类化合物，能在人体富集，对生殖系统、免疫系统、骨代谢等多方面产生严重毒性。近年来，大量动物试验和体外试验已经证实，骨是TCDD的敏感靶点，TCDD能引起骨形态结构、骨密度和骨生物力学等特征的改变。TCDD可通过芳香烃受体（aryl hydrocarbon receptor，AhR）介导的不同信号通路，如RANKL、MAPK、Wnt等影响成骨细胞和破骨细胞的增殖分化，干扰骨代谢，破坏骨重建，诱发骨物理性质的病理改变及骨质疏松等相关骨代谢疾病。此外，TCDD的抗雌激素效应( anti-estrogen effect)也在成骨细胞的生成及骨量丢失中起着重要的调节作用。但目前，TCDD影响骨代谢的机制尚未彻底阐明，并且TCDD所介导的各通路之间的相互作用和联系也有待进一步探究，明确相关的分子机制和信号通路可能会为骨代谢疾病的临床治疗提供新思路。本文将总结TCDD对骨物理特性、骨细胞发育与骨代谢产生的影响，并阐述TCDD可能介导的不同信号通路及机制对成骨细胞、破骨细胞生成的调控作用，为临床研究和治疗提供更系统的理论依据。 |
| 英文摘要: |
| 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a kind of highly toxic dioxin compounds, which can enrich in human body and exert serious toxicity to reproductive system, immune system, bone metabolism, and other aspects. Recently, a lot of animal and in vitro experiments have confirmed that bone is the sensitive target of TCDD. TCDD causes changes in bone structure, bone mineral density, and biomechanical characteristics. TCDD affects the proliferation and differentiation of osteoblasts and osteoclasts, interferes with bone metabolism, destroys bone remodeling, induces pathological changes of bone physical properties and osteoporosis related bone diseases through different signal pathways mediated by aryl hydrocarbon receptor (AhR), such as RANKL, MAPK, Wnt, etc. In addition, the anti-estrogen effect of TCDD also plays an important role in the regulation of osteoblast formation and bone loss. However, at present, the mechanism of TCDD affecting bone metabolism is not completely clear, and the interaction and relationship between TCDD-mediated pathways also need to be further explored. Clarifying the relevant molecular mechanisms and signaling pathways may provide new ideas for clinical treatment of bone metabolic diseases. This article summarizes the effects of TCDD on bone physical properties, bone cell development, and bone metabolism, elaborates the regulatory effects of different signaling pathways and mechanisms mediated by TCDD on osteoblasts and osteoclasts, and provides a more systematic theoretical basis for clinical research and treatment. |
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