Asymptomatic Hyperuricemia Is Associated with Achilles Tendon Rupture through Disrupting the Normal Functions of Tendon Stem/Progenitor Cells

作者全名："Liang, Jingjing; Chen, Biao; Li, Yanmei; Nie, Daibang; Lei, Changbin; Yang, Qing; Zhou, Yiqin; Li, Shenglong; Chen, Shuaizhi; Li, Bin; Shu, Lin; Chen, Liaobin; Wang, Wang"

作者地址："[Liang, Jingjing; Li, Yanmei; Nie, Daibang; Li, Shenglong; Chen, Shuaizhi; Wang, Wang] Chongqing Med Univ, Coll Basic Med, Dept Immunol, Chongqing, Peoples R China; [Liang, Jingjing; Li, Yanmei; Nie, Daibang; Li, Shenglong; Chen, Shuaizhi; Wang, Wang] Chongqing Med Univ, Chongqing Key Lab Basic & Translat Res Tumor Immun, Chongqing, Peoples R China; [Chen, Biao; Li, Bin; Shu, Lin; Chen, Liaobin] Wuhan Univ, Zhongnan Hosp, Dept Orthoped Surg, Div Joint Surg & Sports Med, Wuhan, Peoples R China; [Lei, Changbin] Xiangnan Univ, Dept Orthoped, Affiliated Hosp, Chenzhou, Peoples R China; [Yang, Qing] Huazhong Univ Sci & Technol, Tongji Hosp, Dept Orthopaed Surg, Wuhan, Peoples R China; [Zhou, Yiqin] Naval Med Univ, Shanghai Changzheng Hosp, Dept Orthoped, Shanghai, Peoples R China"

通信作者："Wang, W (通讯作者)，Chongqing Med Univ, Coll Basic Med, Dept Immunol, Chongqing, Peoples R China.; Wang, W (通讯作者)，Chongqing Med Univ, Chongqing Key Lab Basic & Translat Res Tumor Immun, Chongqing, Peoples R China.; Chen, LB (通讯作者)，Wuhan Univ, Zhongnan Hosp, Dept Orthoped Surg, Div Joint Surg & Sports Med, Wuhan, Peoples R China."

来源：STEM CELLS INTERNATIONAL

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000895992500001

JCR分区：Q2

影响因子：4.3

年份：2022

卷号：2022

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："Hyperuricemia is a metabolic disorder that is essential to the development of inflammatory gout, with increasing prevalence over recent years. Emerging clinical findings has evidenced remarkable tendon damage in individuals with longstanding asymptomatic hyperuricemia, yet the impact of hyperuricemia on tendon homeostasis and associated repercussions is largely unknown. Here, we investigated whether asymptomatic hyperuricemia was associated with spontaneous ruptures in the Achilles tendon and the pathological effect of hyperuricemia on the tendon stem/progenitor cells (TSPCs). Significantly higher serum uric acid (SUA) levels were found in 648 closed Achilles tendon rupture (ATR) patients comparing to those in 12559 healthy volunteers. In vitro study demonstrated that uric acid (UA) dose dependently reduced rat Achilles TSPC viability, decreased the expressions of tendon collagens, and deformed their structural organization while significantly increased the transcript levels of matrix degradative enzymes and proinflammatory factors. Consistently, marked disruptions in Achilles tendon tissue structural and functional integrity were found in a rat model of hyperuricemia, together with enhanced immune cell infiltration. Transcriptome analysis revealed a significant elevation in genes involved in metabolic stress and tissue degeneration in TSPCs challenged by hyperuricemia. Specifically, reduced activity of the AKT-mTOR pathway with enhanced autophagic signaling was confirmed. Our findings indicate that asymptomatic hyperuricemia may be a predisposition of ATR by impeding the normal functions of TSPCs. This information may provide theoretical and experimental basis for exploring the early prevention and care of ATR."

基金机构：National Natural Science Foundation of China; [81871779]

基金资助正文：AcknowledgmentsWe thank Dr. Jianying Zhang for assistance in the preparation of this manuscript. This work was supported in part by the National Natural Science Foundation of China (81871779).