國家衛生研究院 NHRI:Item 3990099045/9686
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    題名: CLEC5A is critical for dengue virus-induced osteoclast activation and bone homeostasis
    作者: Huang, YL;Chen, ST;Liu, RS;Chen, YH;Lin, CY;Huang, CH;Shu, PY;Liao, CL;Hsieh, SL
    貢獻者: Division of Infectious Diseases
    摘要: Abstract: Osteoclasts are bone tissue macrophages critical to maintain bone homeostasis. However, whether osteoclasts are susceptible to flaviviral infections and involved in dengue virus (DV)-induced disease pathogenesis is still unknown. In this study, we found that osteoclasts were preferentially susceptible to DV infection and produced similar amounts of cytokines and infectious virions as macrophages. Interestingly, DV-induced cytokine secretion and nuclear translocation of the transcription factor NFATc1 in osteoclast via the Syk-coupled myeloid C-type lectin member 5A (CLEC5A). Moreover, DV caused transient inflammatory reaction in bone tissue and upregulated osteolytic activity to release C-telopeptide of type I collagen (CTX-1) from bone tissue. Furthermore, DV-induced osteolytic activity was attenuated in CLEC5A-deficient mice, and administration of antagonistic anti-CLEC5A mAb inhibited DV-activated osteolytic activity and reduced CTX-1 serum level in vivo. This observation suggests that osteoclasts serve as a novel target for DV, and transient upregulation of osteolytic activity may contribute to the clinical symptoms in dengue patients. Key messages: Cultured osteoclasts were susceptible to DV infection.Osteoclasts produced similar amounts of cytokines and infectious virions as macrophages.DV induced nuclear translocation of NFATc1 in osteoclast via CLEC5A.DV caused transient inflammatory reaction in bone tissue and upregulated osteolytic activity.Antagonistic anti-CLEC5A mAb inhibited DV-activated osteolytic activity in vivo.
    日期: 2016-09
    關聯: Journal of Molecular Medicine. 2016 Sep;94(9):1025-1037.
    Link to: http://dx.doi.org/10.1007/s00109-016-1409-0
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0946-2716&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000382112400008
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84962132758
    顯示於類別:[廖經倫] 期刊論文

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