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

ABSTRACT:

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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.

SUBMITTER: Huang YL

PROVIDER: S-EPMC4992505 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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

Huang Ya-Lang YL Chen Szu-Ting ST Liu Ren-Shyan RS Chen Yen-Hsu YH Lin Chun-Yu CY Huang Chung-Hao CH Shu Pei-Yun PY Liao Ching-Len CL Hsieh Shie-Liang SL

Journal of molecular medicine (Berlin, Germany) 20160331 9

<h4>Unlabelled</h4>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 tra ...[more]

PMID: 27033255

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Dataset Information

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

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Key messages

Publications

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

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