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

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

Journal of molecular medicine (Berlin, Germany) (2016-04-02)
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
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. 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.

MATERIALS
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Brand
Product Description

Sigma-Aldrich
Goat Anti-Mouse IgG Antibody, HRP conjugate, Species Adsorbed, 0.8 mg/mL, Chemicon®
Sigma-Aldrich
Anti-Glyceraldehyde-3-Phosphate Dehydrogenase Antibody, clone 6C5, clone 6C5, Chemicon®, from mouse