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Arthritogenic alphaviral infection perturbs osteoblast function and triggers pathologic bone loss

Chen, Weiqiang; Foo, Suan-Sin; Rulli, Nestor E.; Taylor, Adam; Sheng, Kuo-Ching; Herrero, Lara; Herring, Belinda L.; Lidbury, Brett; Li, Rachel; Walsh, Nicole C.; Sims, Natalie A.; Smith, Paul; Mahalingam, Suresh

Description

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...[Show more]

dc.contributor.authorChen, Weiqiang
dc.contributor.authorFoo, Suan-Sin
dc.contributor.authorRulli, Nestor E.
dc.contributor.authorTaylor, Adam
dc.contributor.authorSheng, Kuo-Ching
dc.contributor.authorHerrero, Lara
dc.contributor.authorHerring, Belinda L.
dc.contributor.authorLidbury, Brett
dc.contributor.authorLi, Rachel
dc.contributor.authorWalsh, Nicole C.
dc.contributor.authorSims, Natalie A.
dc.contributor.authorSmith, Paul
dc.contributor.authorMahalingam, Suresh
dc.date.accessioned2015-12-10T22:31:26Z
dc.identifier.issn0027-8424
dc.identifier.urihttp://hdl.handle.net/1885/55523
dc.description.abstractArthritogenic 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.
dc.publisherNational Academy of Sciences (USA)
dc.rightsAuthor/s retain copyright
dc.sourcePNAS - Proceedings of the National Academy of Sciences of the United States of America
dc.titleArthritogenic alphaviral infection perturbs osteoblast function and triggers pathologic bone loss
dc.typeJournal article
local.description.notesImported from ARIES
local.identifier.citationvolume111
dc.date.issued2014
local.identifier.absfor110309 - Infectious Diseases
local.identifier.absfor110316 - Pathology
local.identifier.ariespublicationu4971216xPUB331
local.type.statusPublished Version
local.contributor.affiliationChen, Weiqiang, Griffith University
local.contributor.affiliationFoo, Suan-Sin, Griffith University
local.contributor.affiliationRulli, Nestor E., Griffith University
local.contributor.affiliationTaylor, Adam, Griffith University
local.contributor.affiliationSheng, Kuo-Ching, Griffith University
local.contributor.affiliationHerrero, Lara, Griffith University
local.contributor.affiliationHerring, Belinda L., Griffith University
local.contributor.affiliationLidbury, Brett, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationLi, Rachel, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationWalsh, Nicole C., The University of Melbourne
local.contributor.affiliationSims, Natalie A., The University of Melbourne
local.contributor.affiliationSmith, Paul, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationMahalingam, Suresh, Griffith University
local.bibliographicCitation.issue16
local.bibliographicCitation.startpage6040
local.bibliographicCitation.lastpage6045
local.identifier.doi10.1073/pnas.1318859111
local.identifier.absseo920109 - Infectious Diseases
dc.date.updated2015-12-09T10:10:35Z
local.identifier.scopusID2-s2.0-84899098157
local.identifier.thomsonID000334694000070
dcterms.accessRightsOpen Access
CollectionsANU Research Publications

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