Effect of age on cytokine response in an experimental model of osteomyelitis

García-Álvarez, F; Navarro-Zorraquino, Marta; Castro, Ángel; Grasa, J.; Pastor, C.; Monzón, Marta; Martínez, Ana Belén; García-Alvarez, Ignacio; Castillo, Jesús; Lozano, Ricardo

doi:10.1007/s10522-008-9211-1

Cited by 14 publications

(9 citation statements)

References 42 publications

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“…IL-1β can be induced in human and murine osteoblasts by a variety of stimuli including TNFα [36], [37], [38]. Indeed increased levels of IL-1β have been detected in several animal models of bone infection [39]. Collectively these results suggest that S. aureus SpA might be mimicking the effects of TNFα by binding to TNFR-1.…”

Section: Discussionmentioning

confidence: 87%

Staphylococcus aureus Protein A Plays a Critical Role in Mediating Bone Destruction and Bone Loss in Osteomyelitis

et al. 2012

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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.

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Section: Discussionmentioning

confidence: 87%

Staphylococcus aureus Protein A Plays a Critical Role in Mediating Bone Destruction and Bone Loss in Osteomyelitis

et al. 2012

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“…A model designed by Lucke et al (Lucke et al , 2003b), though technically more challenging, mimics the human condition more accurately. It requires placement of a Kirschner wire (K-wire) or needle down the length of the medullary canal of the tibia with contamination prior to implanting the metal implant, which has been reproduced by other investigators (Bisland et al , 2006; Garcia-Alvarez et al , 2009; Lucke et al , 2005). Others have modified this technique to include internal fixation of the tibia after performing an osteotomy of the tibial diaphyseal area(Alt et al , 2011).…”

Section: Literature Review Of Animal Modelsmentioning

confidence: 99%

A systematic review of animal models for Staphylococcus aureus osteomyelitis

Reizner¹,

Hunter²,

O’Malley³

et al. 2014

eCM

112

106

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Staphylococcus aureus (S. aureus) osteomyelitis is a significant complication for orthopaedic patients undergoing surgery, particularly with fracture fixation and arthroplasty. Given the difficulty in studying S. aureus infections in human subjects, animal models serve an integral role in exploring the pathogenesis of osteomyelitis, and aid in determining the efficacy of prophylactic and therapeutic treatments. Animal models should mimic the clinical scenarios seen in patients as closely as possible to permit the experimental results to be translated to the corresponding clinical care. To help understand existing animal models of S. aureus, we conducted a systematic search of PubMed and Ovid MEDLINE to identify in vivo animal experiments that have investigated the management of S. aureus osteomyelitis in the context of fractures and metallic implants. In this review, experimental studies are categorised by animal species and are further classified by the setting of the infection. Study methods are summarised and the relevant advantages and disadvantages of each species and model are discussed. While no ideal animal model exists, the understanding of a model's strengths and limitations should assist clinicians and researchers to appropriately select an animal model to translate the conclusions to the clinical setting.

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“…Increased levels of IL-1β have been measured in the tibiae of 22-month-old rats experimentally implanted with S. aureus -infected needles, and the same animals have increased circulating levels of IL-6 (Garcia-Alvarez et al, 2009). In a murine osteomyelitis model, bone levels of IL-1β and IL-6 are significantly increased in the early post-infection period, with TNFα rising later during the infection (Yoshii et al, 2002).…”

Section: Inflammation In Bone Infectionmentioning

confidence: 99%

Interaction of staphylococci with bone

Wright

Nair

2010

International Journal of Medical Microbiology

220

166

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Staphylococci, in particular Staphylococcus aureus, are the predominant cause of bone infections worldwide. These infections are painful, debilitating and with the rise in antibiotic-resistant forms, increasingly difficult to treat. The growth in the number of prosthetic joint replacement procedures also provides new opportunities for these infections to take hold. Comprehending the mechanisms by which staphylococci interact with and damage bone is critical to the development of new approaches to meet this challenge. This review summarises current understanding of the mechanisms by which staphylococci infect and damage bone. We address the role of the inflammatory response to staphylococcal infection in disrupting the homeostatic balance of bone matrix deposition and resorption and thereby mediating bone destruction. A number of virulence factors that have been shown to contribute to bone infection and pathology are discussed, however no single factor has been defined as being specific to bone infections. Although traditionally considered an extracellular pathogen, there is increasing evidence that staphylococci are able to invade host cells, and that an intracellular lifestyle may facilitate long-term persistence in bone tissue, enabling evasion of antimicrobials and host immune responses. ‘Small colony variant’ strains, with mutations disabling the electron transport pathway appear particularly adept at invading and persisting within host cells, and exhibit enhanced antimicrobial resistance, and may represent a further complication in the treatment and management of staphylococcal bone disease.

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Effect of age on cytokine response in an experimental model of osteomyelitis

Cited by 14 publications

References 42 publications

Staphylococcus aureus Protein A Plays a Critical Role in Mediating Bone Destruction and Bone Loss in Osteomyelitis

Staphylococcus aureus Protein A Plays a Critical Role in Mediating Bone Destruction and Bone Loss in Osteomyelitis

A systematic review of animal models for Staphylococcus aureus osteomyelitis

Interaction of staphylococci with bone

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