期刊
JOURNAL OF MOLECULAR MEDICINE-JMM
卷 94, 期 9, 页码 1025-1037出版社
SPRINGER
DOI: 10.1007/s00109-016-1409-0
关键词
Osteoclasts; Dengue virus; Syk-coupled myeloid C-type lectin member 5A (CLEC5A)
资金
- Academia Sinica
- Ministry of Science and Technology [NSC 104-2321-B-001-017, NSC 103-2320-B-001-010-MY3, MOST 104-0210-01-09-02]
- Thematic Research Project of Academia Sinica [AS-101-TP-B06-2]
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.
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