School of Public Health, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, Xi'an Jiaotong University Health Science Center, No.76 Yanta West Road, Xi'an, Shaanxi, 710061, People's Republic of China.
Biol Trace Elem Res. 2017 Oct;179(2):178-184. doi: 10.1007/s12011-017-0964-8. Epub 2017 Feb 21.
Kashin-Beck disease (KBD) is an endemic chronic osteochondral disease characterized by high prevalence, disability, and morbidity and is distributed from the northeast to the southwest in China, in some regions of Eastern Siberia in Russia, and in North Korea. Although the selenium deficiency etiological hypothesis for KBD has been proposed by scientists for decades, the idea that selenium deficiency is one of the most important environmental factors but not the primary and sole pathogenic factor for KBD has been widely accepted. Zn, which is closely involved in the synthesis of enzymes, nucleic acids, and proteins, is an essential microelement in vivo. A conundrum still exists in research on the relationship between Zn and KBD due to inconsistent results, but it has been confirmed that Zn can help repair metaphyseal lesions in patients with KBD, indicating that Zn might play a key role in the pathogenesis of KBD, although the mechanism is unknown. The zinc-ZIP8-MTF1 axis in chondrocytes forms a catabolic cascade that promotes upregulation of the crucial effector matrix-degrading enzymes MMP3, MMP13, and ADAMTS5, thereby leading to osteoarthritis (OA) cartilage destruction. Zinc finger protein-related genes, the ZNT family, and the ZIP family of Zn transporter genes have been found to be differentially expressed in KBD by high-throughput screening. Therefore, Zn could play a key role in the pathogenesis of KBD.
大骨节病（KBD）是一种流行范围广、致残率和发病率高的地方性慢性骨软骨病，在中国从东北到西南呈灶状分布，在俄罗斯东西伯利亚的一些地区和朝鲜也有分布。尽管几十年来科学家们提出了大骨节病的硒缺乏病因假说，但硒缺乏是 KBD 最重要的环境因素之一，但不是原发性和唯一的致病因素这一观点已被广泛接受。Zn 是体内合成酶、核酸和蛋白质所必需的微量元素，与酶的合成、核酸和蛋白质的合成密切相关。由于结果不一致，Zn 与 KBD 之间的关系的研究仍然存在难题，但已经证实 Zn 可以帮助修复 KBD 患者的干骺端病变，这表明 Zn 可能在 KBD 的发病机制中发挥关键作用，尽管其机制尚不清楚。软骨细胞中的锌-ZIP8-MTF1 轴形成一个分解代谢级联，促进关键效应基质降解酶 MMP3、MMP13 和 ADAMTS5 的上调，从而导致骨关节炎（OA）软骨破坏。通过高通量筛选发现，锌指蛋白相关基因、ZNT 家族和 Zn 转运体基因的 ZIP 家族在 KBD 中表达存在差异。因此，Zn 可能在 KBD 的发病机制中发挥关键作用。
