Type

Journal Article

Authors

Steven W Kerrigan
Fergal J O'Brien
Timothy J Foster
Helen Miajlovic
Maghnus O'Seaghdha
Amro Widaa
Tania Claro

Subjects

Microbiology

Topics
osteoprotegerin staphylococcal protein a mice pathology osteomyelitis cell line rank ligand osteoblasts calcification physiologic staphylococcus aureus models biological animals receptors tumor necrosis factor type i bone and bones signal transduction protein binding microbiology apoptosis metabolism cell proliferation

Staphylococcus aureus protein A binds to osteoblasts and triggers signals that weaken bone in osteomyelitis. (2010)

Abstract Osteomyelitis is a debilitating infectious disease of the bone. It is predominantly caused by S. aureus and is associated with significant morbidity and mortality. It is characterised by weakened bones associated with progressive bone loss. Currently the mechanism through which either bone loss or bone destruction occurs in osteomyelitis patients is poorly understood. We describe here for the first time that the major virulence factor of S. aureus, protein A (SpA) binds directly to osteoblasts. This interaction prevents proliferation, induces apoptosis and inhibits mineralisation of cultured osteoblasts. Infected osteoblasts also increase the expression of RANKL, a key protein involved in initiating bone resorption. None of these effects was seen in a mutant of S. aureus lacking SpA. Complementing the SpA-defective mutant with a plasmid expressing spa or using purified protein A resulted in attachment to osteoblasts, inhibited proliferation and induced apoptosis to a similar extent as wildtype S. aureus. These events demonstrate mechanisms through which loss of bone formation and bone weakening may occur in osteomyelitis patients. This new information may pave the way for the development of new and improved therapeutic agents to treat this disease.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Steven W Kerrigan, Fergal J O'Brien, Timothy J Foster, Helen Miajlovic, Maghnus O'Seaghdha, Amro Widaa, Tania Claro

Experts in our system

1
Steven W Kerrigan
Royal College of Surgeons in Ireland
Total Publications: 37
 
2
Fergal J O'Brien
Royal College of Surgeons in Ireland
Total Publications: 265
 
3
Timothy J Foster
Trinity College Dublin
Total Publications: 96
 
4
Amro Widaa
Royal College of Surgeons in Ireland
Total Publications: 13
 
5
Tania Claro
Royal College of Surgeons in Ireland
Total Publications: 13