Staphylococcus aureus protein A enhances osteoclastogenesis via TNFR1 and EGFR signaling

Bertelli, Andrea Cristina Mendoza; Delpino, M. Victoria; Lattar, Santiago M.; Giai, Constanza; Llana, Mariángeles Noto; Sanjuán, Norberto; Cassat, James E.; Sordelli, Daniel O.; Gómez, M. A.

doi:10.1016/j.bbadis.2016.07.016

Cited by 38 publications

(34 citation statements)

References 47 publications

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“…In addition to the typical inflammation symptoms, the most characteristic of these diseases is accompanied by excessive bone destruction and bone non-union (Olson & Horswill, 2013). Previous reports demonstrated that the femoral bone mass was lost about 10-20% in rat models which were infected by S. aureus (Mendoza Bertelli et al, 2016). In case of trauma or surgery, S. aureus could break through the host barrier for local colonization, is extremely easy to produce bacterial biofilm.…”

Section: Discussionmentioning

confidence: 99%

Staphylococcal protein A promotes osteoclastogenesis through MAPK signaling during bone infection

Wang

Liu

Dou

et al. 2017

Journal Cellular Physiology

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Bone infection is a common and serious complication in the orthopedics field, which often leads to excessive bone destruction and non‐union. Osteoclast is the only type of cells which have the function of bone resorption. Its over activation is closely related to excessive bone loss. Staphylococcus aureus (S. aureus) is a major pathogen causing bone infection, which can produce a large number of strong pathogenic substances staphylococcal protein A (SPA). However, few studies were reported about the effects of SPA on osteoclastogenesis. In our study, we observed that S. aureus activated osteoclasts and promoted bone loss in bone infection specimens. Then, we investigated the effects of SPA on RANKL‐induced osteoclastogenesis in vitro, the results revealed that SPA promoted osteoclastic differentiation and fusion, and enhanced osteoclastic bone resorption. In addition, we also showed that SPA upregulated the expression of NFATc1 and c‐FOS through the activation of MAPK signaling to promote osteoclastogenesis. Our findings might help us better understand the pathogenic role of S. aureus in bone infection and develop new therapeutic strategies for infectious bone diseases.

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Section: Discussionmentioning

confidence: 99%

Staphylococcal protein A promotes osteoclastogenesis through MAPK signaling during bone infection

Wang

Liu

Dou

et al. 2017

Journal Cellular Physiology

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“…Studies have demonstrated the over activation of epidermal growth factor receptor (EGFR) signalling in S. aureus ‐infected bone (Chen, Yao, et al, 2018; Mendoza Bertelli et al, 2016). Epidermal growth factor receptor (EGFR) is a key molecule regulating cell survival (Liu et al, 2019; Zhang et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

EGFR / FAK and c‐Src signalling pathways mediate the internalisation of Staphylococcus aureus by osteoblasts

Hou

et al. 2020

Cellular Microbiology

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Internalisation of Staphylococcus aureus in osteoblasts plays a critical role in the persistence and recurrence of osteomyelitis, the mechanisms involved in this process remain largely unknown. In the present study, evidence of internalised S. aureus in osteoblasts was found in long bone of haematogenous osteomyelitis in mice after 2 weeks of infection. Meanwhile, eliminating extracellular S. aureus by gentamicin can partially rescue bone loss, whereas the remaining intracellular S. aureus in osteoblasts may be associated with continuous bone destruction. In osteoblastic MC3T3 cells, intracellular S. aureus was detectable as early as 15 min after infection, and the internalisation rates increased with the extension of infection time. Additionally, S. aureus invasion stimulated the expression of phosphor‐focal adhesion kinase (FAK), phosphor‐epidermal growth factor receptor (EGFR) and phosphor‐c‐Src in a time‐dependent way, and blocking EGFR/FAK or c‐Src signalling significantly reduced the internalisation rate of S. aureus in osteoblasts. Our findings provide new insights into the mechanism of S. aureus internalisation in osteoblast and raise the potential of targeting EGFR/FAK and c‐Src as adjunctive therapeutics for treating chronic S. aureus osteomyelitis.

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“…Although the primary function of SpA is immune evasion, studies have documented its direct role in bone infection. It was shown that SpA can directly bind to osteoblasts, mediating cell death, inhibition of bone formation (osteogenesis), and induction of bone resorption (osteoclastogenesis) (51)(52)(53)(54). The importance of osteoclastic activity in osteomyelitis is becoming evident, and therefore many studies have emerged to examine the effects of S. aureus in promoting osteoclastogenesis and osteoclastic activity.…”

Section: Staphylococcal Colonization Of Bonementioning

confidence: 99%

Staphylococcal Osteomyelitis: Disease Progression, Treatment Challenges, and Future Directions

et al. 2018

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Osteomyelitis is an inflammatory bone disease that is caused by an infecting microorganism and leads to progressive bone destruction and loss. The most common causative species are the usually commensal staphylococci, with and responsible for the majority of cases. Staphylococcal infections are becoming an increasing global concern, partially due to the resistance mechanisms developed by staphylococci to evade the host immune system and antibiotic treatment. In addition to the ability of staphylococci to withstand treatment, surgical intervention in an effort to remove necrotic and infected bone further exacerbates patient impairment. Despite the advances in current health care, osteomyelitis is now a major clinical challenge, with recurrent and persistent infections occurring in approximately 40% of patients. This review aims to provide information about staphylococcus-induced bone infection, covering the clinical presentation and diagnosis of osteomyelitis, pathophysiology and complications of osteomyelitis, and future avenues that are being explored to treat osteomyelitis.

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Staphylococcus aureus protein A enhances osteoclastogenesis via TNFR1 and EGFR signaling

Cited by 38 publications

References 47 publications

Staphylococcal protein A promotes osteoclastogenesis through MAPK signaling during bone infection

Staphylococcal protein A promotes osteoclastogenesis through MAPK signaling during bone infection

EGFR / FAK and c‐Src signalling pathways mediate the internalisation of Staphylococcus aureus by osteoblasts

Staphylococcal Osteomyelitis: Disease Progression, Treatment Challenges, and Future Directions

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