ECTS2013 Poster Presentations Cell biology: osteoclasts and bone resorption (24 abstracts)
Osteoclasts activity is affected by adenovirus infection
Ana Isabel Espirito Santo 1 , Lynett Danks 2 , David Mahoney 3 , Youridies Vattakuzhi 1 , Afsaneh Sabokbar 3 & Nicole Horwood 1
1Kennedy Institute of Rheumatology, London, UK; 2Tokyo Medical and Dental University, Yushima, Japan; 3Botnar Research Centre, Oxford, UK.
Osteoclast resorption depends on their ability to reorganise their actin cytoskeleton and form the sealing zone. In order to resorb bone, osteoclasts become polarised by condensing their podosomes into a highly dynamic podosomal belt. The podosome turnover is regulated by several factors such as non-receptor tyrosine kinases, small GTPases and actin-binding proteins. The innate immune system responds to viral pathogens. Cytoplasmic double-stranded DNA activates the immune system inducing IFN (interferon) production, inflammasome activation, and cell death. We studied whether transfecting osteoclasts with DNA affected their differentiation and resorption ability. The differentiation and activity of adenovirus infected human osteoclasts was determined relative to non-infected cells. By analysing the formation of TRAP positive cells, no effect on osteoclasts differentiation was observed however, a reduction in resorption was found. Early infection significantly inhibited osteoclasts resorption compared to late infection. MTT cell viability assay determined no effect on osteoclast cell viability following transfection. Interestingly, an increased in TSG-6 (tumor necrosis factor stimulated gene-6) expression was observed in infected osteoclasts. TSG-6 expression is known to be induced in response to inflammatory cytokines and to downregulate osteoclasts activity.
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