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

Wen-Jiao Wu,1,* Chang-Liang Xia,1,* Shuan-Ji Ou,1 Yang Yang,1 Xiao-Zhong Zhou,1 Yun-Fei Ma,2 Yi-Long Hou,2 Fa-Zheng Wang,3 Qing-Po Yang,3 Yong Qi,1,4 Chang-Peng Xu1,4 1Department of Orthopaedics, Guangdong Second Provincial General Hospital, Guangzhou, Guangdong, People’s Republic of China; 2Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 3Department of Orthopaedics, First People’s Hospital of Kashgar Prefecture, Kashgar, Xinjiang, People’s Republic of China; 4The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yong Qi; Chang-Peng Xu, Tel +86-20-8916-8085, Email gd2hqy@163.com; gd2hxcp@163.comIntroduction: 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 aureusis 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.Keywords: NBD peptide, bone infection, Staphylococcus aureus, osteomyelitis