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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Taylor, Adam Foo, Suan-sin Herring, Belinda L. Rulli, Nestor E. Smith, Paul N. Mahalingam, Suresh Chen, Weiqiang Lidbury, Brett A. Sheng, Kuo-ching Herrero, Lara J. Sims, Natalie A. Walsh, Nicole C. Li, Rachel W. |
| Description | Author Affiliation: Chen W ( Emerging Viruses and Inflammation Research Group, Institute for Glycomics, Griffith University, Gold Coast, QLD 4222, Australia.); |
| Abstract | Arthritogenic alphaviruses including Ross River virus (RRV), Sindbis virus, and chikungunya virus cause worldwide outbreaks of musculoskeletal disease. The ability of alphaviruses to induce bone pathologies remains poorly defined. Here we show that primary human osteoblasts (hOBs) can be productively infected by RRV. RRV-infected hOBs produced high levels of inflammatory cytokine including IL-6. The RANKL/OPG ratio was disrupted in the synovial fluid of RRV patients, and this was accompanied by an increase in serum Tartrate-resistant acid phosphatase 5b (TRAP5b) levels. Infection of bone cells with RRV was validated using an established RRV murine model. In wild-type mice, infectious virus was detected in the femur, tibia, patella, and foot, together with reduced bone volume in the tibial epiphysis and vertebrae detected by microcomputed tomographic (µCT) analysis. The RANKL/OPG ratio was also disrupted in mice infected with RRV; both this effect and the bone loss were blocked by treatment with an IL-6 neutralizing antibody. Collectively, these findings provide previously unidentified evidence that alphavirus infection induces bone loss and that OBs are capable of producing proinflammatory mediators during alphavirus-induced arthralgia. The perturbed RANKL/OPG ratio in RRV-infected OBs may therefore contribute to bone loss in alphavirus infection. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 16 |
| Volume Number | 111 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2014-04-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Alphavirus Infections Pathology Virology Arthritis Bone Resorption Osteoblasts Ross River Virus Physiology Acid Phosphatase Blood Animals Antibodies, Neutralizing Pharmacology Bone And Bones Growth Plate Drug Effects Inflammation Mediators Metabolism Interleukin-6 Biosynthesis Isoenzymes Mice Mice, Inbred C57BL Neutralization Tests Osteoclasts Osteogenesis Osteoprotegerin Phenotype RANK Ligand Synovial Fluid Virus Replication X-Ray Microtomography Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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