Purified staphylococcal culture medium stimulates neutral metalloprotease secretion from human articular cartilage

Abstract

Human articular cartilage released significantly increased levels of metal-dependent enzymes capable of degrading collagen, casein, and gelatin at a neutral pH following exposure to a sterile, purified fraction of Staphylococcus aureus culture medium. Neutral metalloprotease activity was determined by radiolabeled substrate assays and substrate gel analysis. The enzymes were activated with 4-aminophenylmercuric acetate and were inhibited by 1,10-phenanthroline and ethylenediamine tetraacetic acid. Protein immunoblots demonstrated that type I collagenase and stromelysin (matrix metalloproteinase III) secretion was increased following staphylococcal medium challenge. The profile of enzymatic activity induced by staphylococcal medium was directly comparable to that observed with interleukin-1, which was used as a positive control. The staphylococcal medium had no inherent proteolytic activity. Increased production of the neutral metalloproteases collagenase and stromelysin may significantly contribute to the extensive cartilage destruction noted in staphylococcal septic arthritis.

Effects of the Hydroxamic Acid Derivate Ro 31-4724 on the Metabolism and Morphology of lnterleukin-1 -Treated Cartilage Explants

“…MMP-2 and MV1P-3. as has been shown by Williams et al [34] and by us (data not shown), as well as proba bly other MMP-proteoglycanases. We chose a crude enzyme solution containing several MMP-proteoglycanases in order to determine whether Ro 31-4724 is a broad-spectrum in hibitor of MM P-protcoglvcanascs able to effi ciently block the PG loss mediated by several MMPs.…”

Inhibition of nitric oxide can ameliorate apoptosis and modulate matrix protein gene expression in bacteria infected chondrocytes in vitro

“…It is possible that bacterial infection elicits a complex response that can not be manipulated by modification of a single pathway. Other bacterial toxins such as staphylococcal proteoglycanreleasing factor [25,26] and reactive oxygen species might also participate in the triggering of various cellular responses in bacteria-infected chondrocytes since both would be upregulated after infection and inhibition of their production could lessen the severity of arthritis [14,19]. However, it is important to emphasize that this study is a simplified in vitro model without consideration of extracellular matrix, synovial tissue, and other inflammatory cells.…”

Joint infection

“…The bacteria itself can secrete a factor that accelerates the loss of proteoglycan from cartilage (Smith and Schurman 1986). The loss of proteoglycan is associated with increase in chondrocyte-derived neutral metalloproteinases (Williams et al 1991 ). Bacteria that have a collagen receptor can mediate adhesion and add to the virulence of the organism (Witalski et al 1993).…”