STAPHYLOCOCCUS AUREUS PROTEIN A AS A POTENTIAL TARGET TO CONTROL OSTEOCLASTOGENESIS DURING CHRONIC OSTEOMYELITIS

MENDOZA BERTELI ANDREA; DELPINO M. VICTORIA; SORDELLI DANIEL; GOMEZ MARISA

Congreso; LIX REUNIÓN CIENTÍFICA ANUAL Sociedad Argentina de Investigación Clínica LXII REUNIÓN ANUAL Sociedad Argentina de Inmunología; 2014

Staphylococcus aureus is one of the most prevalent pathogenthat causes osteomyelitis in adults. S. aureus protein A (SpA) is avirulence factor that interacts with the TNF receptor 1 and mimicsTNF-α signaling. Given the importance of TNF-α in the inductionof osteoclast differentiation and the regulation of bone metabolism,we hypothesize that SpA may contribute to increase osteoclastogenesis.Bone marrow-derived macrophages (BMM) were stimulatedwith SpA, S. aureus or the isogenic spa- mutant in the presenceof M-CSF during 9 days and multinucleated TRAP positive cellswere enumerated. A significant increase in the number of cellsdifferentiated to osteoclasts (OC) in response to SpA (p<0,001)and S. aureus (p<0.01) was observed. Osteoclastogenesis wassignificantly lower in cells stimulated with the spa- mutant (p<0.05)and in cells stimulated with S. aureus in the presence of an antiproteinA antibody (α-SpA ab) (p<0.05). Similar results were obtainedusing human monocytes as a source of osteoclast precursors.S. aureus induced a significant increase in the levels of RANKand CK expression (p<0.05; p<0.01) molecules that are known tobe highly expressed in osteoclasts, whereas their induction wassignificantly decreased in response to the spa- mutant (p<0.05;p<0.01). An increase in MMP9 gelatinase activity was observedby zymography in supernatants from S. aureus stimulated cellswhereas the MMP9 activity was lower in response to the spamutant.Moreover, a reduction in MMP9 activity in supernatantsfrom cells stimulated with S. aureus in the presence of an α-SpAab was observed. Osteoclasts differentiated in response to S.aureus were able to resorb dentine whereas cells stimulated in thepresence of the spa- mutant did not form resorption pits. Theseresults suggest that S. aureus protein A significantly contributesto osteoclast differentiation and it may play a critical role in theincreased bone resorption that occurs during chronic osteomyelitis.