title: Zinc: the Other Suspected Environmental Factor in Kashin-Beck Disease in Addition to Selenium.
abstract: 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. Zn2+, 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 Zn2+and KBD due to inconsistent results, but it has been confirmed that Zn2+can help repair metaphyseal lesions in patients with KBD, indicating that Zn2+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 Zn2+transporter genes have been found to be differentially expressed in KBD by high-throughput screening. Therefore, Zn2+could play a key role in the pathogenesis of KBD.
authors.affiliation: 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.
authors.forename: Xi
authors.initials: X
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Ning
authors.affiliation: 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.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Yu
authors.affiliation: 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. guox@mail.xjtu.edu.cn.
authors.forename: Xiong
authors.initials: X
authors.lastname: Guo
mesh_terms: D027682:Cation Transport Proteins / Q000378:metabolism; D019902:Chondrocytes / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004781:Environmental Exposure / Q000009:adverse effects* / Q000032:analysis; D006801:Humans; D057767:Kashin-Beck Disease / Q000188:drug therapy / Q000209:etiology*; D055034:Osteochondrosis / Q000378:metabolism; D012643:Selenium / Q000172:deficiency*; D012989:Soil Pollutants / Q000633:toxicity; D014157:Transcription Factors / Q000378:metabolism; D015032:Zinc / Q000032:analysis / Q000378:metabolism* / Q000494:pharmacology / Q000633:toxicity*; D000097809:Transcription Factor MTF-1
chemical_list: D027682:Cation Transport Proteins; D004268:DNA-Binding Proteins; D012643:Selenium; D012989:Soil Pollutants; D014157:Transcription Factors; D015032:Zinc; D000097809:Transcription Factor MTF-1; C530151:SLC39A8 protein, human
keywords: Kashin-Beck disease; Osteoarthritis; Zinc-ZIP8-MTF1 axis; Zn2+ deficiency