NEMO‑binding domain peptide ameliorates inflammatory bone destruction in a Staphylococcus�aureus‑induced chronic osteomyelitis model

Lan, Yanhua; Xie, Hujun; Shi, Yang; Jin, Qianrui; Zhang, Xiaolei; Wang, Yu; Xie, Zhijian

doi:10.3892/mmr.2019.9975

Cited by 8 publications

(7 citation statements)

References 27 publications

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“…Chronic osteomyelitis (COM) is a chronic bone infection characterized by progressive osteonecrosis and dead bone formation, which is closely related to the persistent infectious inflammation after infection (1). A variety of studies have shown that COM patients have disordered T lymphocyte proliferation, and clinical and animal studies also reveal that IL-2 expression and CD4+CD25+Foxp3 Treg cells increase in the peripheral blood in case of COM.…”

Section: Introductionmentioning

confidence: 99%

Immunoregulatory role of IL-2/STAT5/CD4+CD25+Foxp3 Treg pathway in the pathogenesis of chronic osteomyelitis

Mao¹,

Shang-Guan²,

Chen³

et al. 2019

Ann. Transl. Med.

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Background: This study aimed to investigate immunoregulatory role of IL-2/STAT5/CD4+CD25+Foxp3 Treg pathway in pathogenesis of chronic osteomyelitis (COM). Methods: Sprague-Dawley (SD) rats were injected with Staphylococcus aureus to establish COM model. 4 weeks later, the lesioned bones were collected and subjected to HE staining for examination of inflammatory infiltration. Enzyme-linked immunosorbent assay (ELISA) was employed to detect IL-2 expression in peripheral blood; flow cytometry was performed to detect CD25+CD4+Foxp3 Treg cells in peripheral blood. The mRNA expression of Foxp3 and CTLA-4 was detected by RT-PCR and the protein expression of STAT5 and p-STAT5 was detected by Western Blotting in CD25+CD4+Foxp3 Treg cells. Results: In COM group, the periosteal thickening was observed in femur, and there were a large number of inflammatory cells in medullary cavity, accompanied by bone destruction. At 1, 2 and 4 weeks, IL-2 expression significantly increased, the proportion of CD4+CD25+FoxP3 Treg cells in peripheral monocytes markedly increased, the mRNA expression of Foxp3 and CTLA-4 and p-STAT5 protein expression increased dramatically in Treg cells as compared to control group (P<0.001). Conclusions: IL-2/STAT5/CD4+CD25+Foxp3 Treg pathway may be involved in the pathogenesis of COM, and excessive immunosuppression may lead to persistent infectious inflammation, which may become a key target for future treatment of COM.

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Section: Introductionmentioning

confidence: 99%

Immunoregulatory role of IL-2/STAT5/CD4+CD25+Foxp3 Treg pathway in the pathogenesis of chronic osteomyelitis

Mao¹,

Shang-Guan²,

Chen³

et al. 2019

Ann. Transl. Med.

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“…NBD peptides have been reported to modulate inflammation and osteoclastogenesis. 29 , 34 Based on our previous study, NBD peptides also promoted osteoblast differentiation impaired by TNFα. A possible underlying mechanism is that NBD peptides selectively attenuate the activation of NFκB by targeting NEMO and further abrogate (at least partly) the inhibitory effect of inflammation on osteoblast differentiation.…”

Section: Discussionmentioning

confidence: 93%

“…Osteomyelitis is an acute or chronic infection of the bone characterized by suppurative inflammation, abnormal bone remodeling, and uncontrolled bone defects. 34 Antibiotic selection is still considered a difficult cure for osteomyelitis, although the risks of adverse reactions due to prolonged and widespread use of antibiotics have been discussed. S. aureus is the most common cause of bone infection.…”

Section: Discussionmentioning

confidence: 99%

Prophylactic Effects of NFκB Essential Modulator–Binding Domain Peptides on Bone Infection: An Experimental Study in a Rabbit Model

Wu¹,

Xia²,

Ou³

et al. 2022

JIR

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Introduction Osteomyelitis is characterized by intensive inflammatory bone disease and remains a clinical challenge in orthopedic surgery, despite the advances made in medical and surgical therapies. Staphylococcus aureus is a major causative agent of osteomyelitis, causing the progressive inflammatory destruction of bone. Prophylaxis of osteomyelitis during orthopedic surgery is necessary. NFκB essential modulator–binding domain (NBD) peptides are cell-permeable peptide inhibitors of the IκB-kinase complex. The prophylactic effect of NBD peptides in relieving inflammation and inhibiting bone defects in osteomyelitis is still under investigation. Our purpose was to determine the preventive effect of NBD peptides in S. aureus infection–induced bone defects in osteomyelitis. Methods An S. aureus osteomyelitis rabbit model was used in this study. The rabbits were divided into four groups: NBD, cefazolin, control, and PBS. Clinical and laboratory indicators of erythrocyte-sedimentation rate, CRP, and TNFα levels were assessed to monitor systemic reactions. The efficacy of NBD peptides in S. aureus –induced osteomyelitis was evaluated by radiological, histological, and microbiological examinations, immunohistochemistry, immunofluorescence, and micro-CT scans. Results In general, NBD peptides effectively reduced clinical signs in rabbits when compared with the control group. Radiography indicated that there was more severe osteomyelitis in the bacterium-infection control group. There was no significance between cefazolin- and NBD-group average scores. The histological results of the lesion slices further confirmed different severity among the groups. Additionally, significant pathological differences were found between the cefazolin and NBD groups, and the PBS group showed no obvious pathological changes. Conclusion Prophylactic administration of NBD peptides to bone-defect areas inhibited bacterial spread and promoted bone regeneration, making NBD peptides a possible treatment option for prophylaxis in bone infections.

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“…Historically and currently, the most utilized models are long bone models, including tibial ( 115 – 121 ), femoral ( 49 , 122 – 124 ), and radial ( 125 – 129 ). Alternative models such as joint prostheses ( 130 , 131 ), mandibular defects ( 132 ), vertebral models ( 133 – 136 ) and implant infection via hematogenous seeding ( 137 ) exist. Induction of osteomyelitis among these various models can be accomplished via mechanical trauma, either defect ( 117 ) or fracture ( 49 ) creation and bacterial contamination with or without application of a sclerosing agent or foreign body placement ( 115 ), or through placement of contaminated implants ( 49 , 129 ).…”

Section: Small Animal Modelsmentioning

confidence: 99%

Role of Animal Models to Advance Research of Bacterial Osteomyelitis

Billings

Anderson

2022

Front. Vet. Sci.

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Osteomyelitis is an inflammatory bone disease typically caused by infectious microorganisms, often bacteria, which causes progressive bone destruction and loss. The most common bacteria associated with chronic osteomyelitis is Staphylococcus aureus. The incidence of osteomyelitis in the United States is estimated to be upwards of 50,000 cases annually and places a significant burden upon the healthcare system. There are three general categories of osteomyelitis: hematogenous; secondary to spread from a contiguous focus of infection, often from trauma or implanted medical devices and materials; and secondary to vascular disease, often a result of diabetic foot ulcers. Independent of the route of infection, osteomyelitis is often challenging to diagnose and treat, and the effect on the patient's quality of life is significant. Therapy for osteomyelitis varies based on category and clinical variables in each case. Therapeutic strategies are typically reliant upon protracted antimicrobial therapy and surgical interventions. Therapy is most successful when intensive and initiated early, although infection may recur months to years later. Also, treatment is accompanied by risks such as systemic toxicity, selection for antimicrobial drug resistance from prolonged antimicrobial use, and loss of form or function of the affected area due to radical surgical debridement or implant removal. The challenges of diagnosis and successful treatment, as well as the negative impacts on patient's quality of life, exemplify the need for improved strategies to combat bacterial osteomyelitis. There are many in vitro and in vivo investigations aimed toward better understanding of the pathophysiology of bacterial osteomyelitis, as well as improved diagnostic and therapeutic strategies. Here, we review the role of animal models utilized for the study of bacterial osteomyelitis and their critically important role in understanding and improving the management of bacterial osteomyelitis.

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NEMO‑binding domain peptide ameliorates inflammatory bone destruction in a Staphylococcus�aureus‑induced chronic osteomyelitis model

Cited by 8 publications

References 27 publications

Immunoregulatory role of IL-2/STAT5/CD4+CD25+Foxp3 Treg pathway in the pathogenesis of chronic osteomyelitis

Immunoregulatory role of IL-2/STAT5/CD4+CD25+Foxp3 Treg pathway in the pathogenesis of chronic osteomyelitis

Prophylactic Effects of NFκB Essential Modulator–Binding Domain Peptides on Bone Infection: An Experimental Study in a Rabbit Model

Role of Animal Models to Advance Research of Bacterial Osteomyelitis

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