STAPHYLOCOCCUS AUREUS PRODUCES A SOLUBLE FACTOR THAT PROMOTES OSTEOCLAST FORMATION

Abstract

Osteomyelitis commonly causes bone destruction and is most frequently due to infection by Staphylococcus aureus. S. aureus is known to secrete a number of surface-associated proteins which are extremely potent stimulators of bone resorption in the mouse calvarial assay system. The precise cellular and humoral mechanisms whereby this stimulatory effect is mediated, in particular whether osteoclast formation or activity is directly promoted by these factors, have not been determined by this study. Surface-associated material (SAM)(0.001ug/ml)obtained from 24 hour cultures of S. aureus was added to cultures of mouse and human osteoclast precursors (RAW 264.7 cells and human peripheral blood mononuclear cells respectively). These cultures were incubated in the presence and absence of receptor activator of nuclear factor kappa B ligand (RANKL) and macrophage colony stimulating factor (M-CSF). It was found that independent of RANKL, SAM was capable of inducing osteoclast formation in cultures of RAW cells and human monocytes. This was evidenced by the generation of tartrate-resistant acid phosphatase-positive multinucleated cells, which formed lacunar resorption pits when these cells were cultured on dentine slices. In cultures where M-CSF, RANKL and SAM were added, osteoclast formation was increased, but did not exceed the osteoclast formation in cultures with M-CSF and RANKL. These findings indicate that S. aureus produces a soluble factor which can promote osteoclast formation. Identification of this factor may help to develop therapeutic strategies for treating bone destruction due to Staphylococcal osteomyelitis.