CLEC5A is critical for dengue virus-induced osteoclast activation and bone homeostasis

Ya Lang Huang, Szu Ting Chen, Ren Shyan Liu, Yen Hsu Chen, Chun Yu Lin, Chung Hao Huang, Pei Yun Shu, Ching Len Liao, Shie Liang Hsieh

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10 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1-13
Number of pages13
JournalJournal of Molecular Medicine
DOIs
Publication statusAccepted/In press - Mar 31 2016

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Keywords

  • Dengue virus
  • Osteoclasts
  • Syk-coupled myeloid C-type lectin member 5A (CLEC5A)

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery
  • Genetics(clinical)

Cite this

Huang, Y. L., Chen, S. T., Liu, R. S., Chen, Y. H., Lin, C. Y., Huang, C. H., Shu, P. Y., Liao, C. L., & Hsieh, S. L. (Accepted/In press). CLEC5A is critical for dengue virus-induced osteoclast activation and bone homeostasis. Journal of Molecular Medicine, 1-13. https://doi.org/10.1007/s00109-016-1409-0