Bindarit, an inhibitor of monocyte chemotactic protein synthesis, protects against bone loss induced by Chikungunya virus infection

Abstract

Objectives. Arthritogenic alphaviruses including Ross River virus (RRV), Sindbis virus (SINV) and chikungunya virus (CHIKV) are generally associated with outbreaks of polyarthritis. Alphavirus endemics can infect many people. Patients with underlying arthroses, such as osteoarthritis (OA), are potentially at risk of disease exacerbation. We validated a mouse model of RRV infection of bone cells and compared the susceptibility and response of primary human osteoblasts from healthy and OA individuals to RRV infection. Hypothesis (?) Methods. Mice were infected with RRV and virus localisation in bone was determined using immunohistochemistry. Primary human osteoblasts were isolated from trabecular bone fragments from healthy and OA individuals and infected with RRV. The effects of RRV infection in human osteoblasts were determined by flow cytometry, plaque assays, enzyme-linked immunosorbent assay, and real-time polymerase chain reaction. Results. Primary osteoblasts were susceptible to RRV infection and supported production of infectious virus. RANKL expression was increased and OPG expression was suppressed in osteoblasts after RRV infection. Osteoblasts were major producers of inflammatory cytokines, including IL-6, IL-1ߠand MCP-1 in response to RRV infection. Osteoblasts from OA patients had increased susceptibility to infection. There was also a greater expression of bone-resorbing and pro-inflammatory factors, but lower RIG-I and IFN-ߠexpression compared to cells from healthy donors. Conclusions. Osteoblasts are highly susceptible to RRV infection. Susceptibility to infection and production of pro-inflammatory mediator are increased in osteoblasts from OA patients, suggesting a mechanism for exacerbation of disease in OA patients infected with RRV.