Asymptomatic Hyperuricemia Is Associated with Achilles Tendon Rupture through Disrupting the Normal Functions of Tendon Stem/Progenitor Cells
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 hyperuricemi...
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| Format: | Article |
| Language: | English |
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Wiley
2022-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2022/6795573 |
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| author | Jingjing Liang Biao Chen Yanmei Li Daibang Nie Changbin Lei Qing Yang Yiqin Zhou Shenglong Li Shuaizhi Chen Bin Li Lin Shu Liaobin Chen Wang Wang |
| author_facet | Jingjing Liang Biao Chen Yanmei Li Daibang Nie Changbin Lei Qing Yang Yiqin Zhou Shenglong Li Shuaizhi Chen Bin Li Lin Shu Liaobin Chen Wang Wang |
| author_sort | Jingjing Liang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-57131dd1ea6e4c709d89b7e162c05096 |
| institution | Kabale University |
| issn | 1687-9678 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-57131dd1ea6e4c709d89b7e162c050962025-02-03T05:57:25ZengWileyStem Cells International1687-96782022-01-01202210.1155/2022/6795573Asymptomatic Hyperuricemia Is Associated with Achilles Tendon Rupture through Disrupting the Normal Functions of Tendon Stem/Progenitor CellsJingjing Liang0Biao Chen1Yanmei Li2Daibang Nie3Changbin Lei4Qing Yang5Yiqin Zhou6Shenglong Li7Shuaizhi Chen8Bin Li9Lin Shu10Liaobin Chen11Wang Wang12Department of ImmunologyDivision of Joint Surgery and Sports MedicineDepartment of ImmunologyDepartment of ImmunologyDepartment of OrthopedicsDepartment of Orthopaedic SurgeryDepartment of OrthopedicsDepartment of ImmunologyDepartment of ImmunologyDivision of Joint Surgery and Sports MedicineDivision of Joint Surgery and Sports MedicineDivision of Joint Surgery and Sports MedicineDepartment of ImmunologyHyperuricemia 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.http://dx.doi.org/10.1155/2022/6795573 |
| spellingShingle | Jingjing Liang Biao Chen Yanmei Li Daibang Nie Changbin Lei Qing Yang Yiqin Zhou Shenglong Li Shuaizhi Chen Bin Li Lin Shu Liaobin Chen Wang Wang Asymptomatic Hyperuricemia Is Associated with Achilles Tendon Rupture through Disrupting the Normal Functions of Tendon Stem/Progenitor Cells Stem Cells International |
| title | Asymptomatic Hyperuricemia Is Associated with Achilles Tendon Rupture through Disrupting the Normal Functions of Tendon Stem/Progenitor Cells |
| title_full | Asymptomatic Hyperuricemia Is Associated with Achilles Tendon Rupture through Disrupting the Normal Functions of Tendon Stem/Progenitor Cells |
| title_fullStr | Asymptomatic Hyperuricemia Is Associated with Achilles Tendon Rupture through Disrupting the Normal Functions of Tendon Stem/Progenitor Cells |
| title_full_unstemmed | Asymptomatic Hyperuricemia Is Associated with Achilles Tendon Rupture through Disrupting the Normal Functions of Tendon Stem/Progenitor Cells |
| title_short | Asymptomatic Hyperuricemia Is Associated with Achilles Tendon Rupture through Disrupting the Normal Functions of Tendon Stem/Progenitor Cells |
| title_sort | asymptomatic hyperuricemia is associated with achilles tendon rupture through disrupting the normal functions of tendon stem progenitor cells |
| url | http://dx.doi.org/10.1155/2022/6795573 |
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