Abstract
Staphylococcus aureus is the most frequent causative organism of osteomyelitis. It is characterised by widespread bone loss and bone destruction. Previously we demonstrated that S. aureus protein A (SpA) is capable of binding to tumour necrosis factor receptor-1 expressed on pre-osteoblastic cells, which results in signal generation that leads to cell apoptosis resulting in bone loss. In the current report we demonstrate that upon S. aureus binding to osteoblasts it also inhibits de novo bone formation by preventing expression of key markers of osteoblast growth and division such as alkaline phosphatase, collagen type I, osteocalcin, osteopontin and osteocalcin. In addition, S. aureus induces secretion of soluble RANKL from osteoblasts which in turn recruits and activates the bone resorbing cells, osteoclasts. A strain of S. aureus defective in SpA failed to affect osteoblast growth or proliferation and most importantly failed to recruit or activate osteoclasts. These results suggest that S. aureus SpA binding to osteoblasts provides multiple coordinated signals that accounts for bone loss and bone destruction seen in osteomyelitis cases. A better understanding of the mechanisms through which S. aureus leads to bone infection may improve treatment or lead to the development of better therapeutic agents to treat this notoriously difficult disease.
Highlights
Bone tissue is composed of both mineral and organic material designed for strength and rigidity to support the loadbearing structure of the body
This was in order to demonstrate that S. aureus still inhibits proliferation in the presence of an extra cellular matrix produced by osteoblasts and that S. aureus protein A (SpA)/TNFR1 interaction occurs despite the presence of a matrix
SpA surface expression was confirmed on S. aureus strains Newman wildtype and the complemented strain, while Newman DSpA was deficient in this protein
Summary
Bone tissue is composed of both mineral and organic material designed for strength and rigidity to support the loadbearing structure of the body. Bone is constantly undergoing remodelling from birth to death This is a complex process involving bone formation followed by bone resorption. The bone remodelling process is tightly controlled by the coupled action of osteoblasts and osteoclasts that sequentially carry out formation of new bone followed by resorption of old bone [1]. Bone formation results from a complex cascade of events that involve proliferation of primitive mesenchymal stem cells, differentiation into matrix forming osteoblasts and mineralisation. Receptor activator of nuclear factor (NF)-kB ligand (RANKL) is the dominating cytokine regulating osteoclast differentiation and proliferation (osteoclastogenesis). It is produced predominantly by osteoblasts in membrane-bound and soluble forms [7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
