Department of Oral Medicine, Affiliated Hospital of Stomatology, Medical College, Zhejiang University, Hangzhou, Zhejiang 310058, P.R. China.
Department of General Dentistry, Hangzhou Dental Hospital, Hangzhou, Zhejiang 310006, P.R. China.
Mol Med Rep. 2019 Apr;19(4):3291-3297. doi: 10.3892/mmr.2019.9975. Epub 2019 Feb 20.
Osteomyelitis, which is characterized by progressive inflammatory bone destruction and resorption, is a difficult‑to‑treat infection. Staphylococcus aureus (S. aureus) is one of the major causes of this disease. This pathogenic microorganism possesses several characteristics, which facilitate its involvement in the occurrence and progression of osteomyelitis. A cell‑permeable peptide inhibitor of the IκB kinase complex, the nuclear factor (NF)‑κB essential modulator‑binding domain (NBD) peptide, has been reported to block osteoclastogenesis and may be considered a potential strategy for preventing inflammatory bone resorption. However, it remains to be determined as to whether the NBD peptide can regulate inflammation and bone resorption in S. aureus‑induced osteomyelitis. In order to investigate the role of NBD in S. aureus‑induced osteomyelitis, the present study obtained the NBD peptide, and confirmed that it inhibited receptor activator of NF‑κB ligand‑induced osteoclastogenesis in vitro. Subsequently, a bone defect was generated and S. aureus was injected into the mandible of experimental animals, in order to establish an in vivo osteomyelitis model. The present study analyzed the following three experimental groups: Untreated, treated with debridement, and treated with debridement plus NBD peptide administration. The results revealed that treatment with the NBD peptide reduced the bone defect in a 3‑dimensional manner, and reduced bone resorption. To the best of our knowledge, the present study is the first to demonstrate that, in a model of osteomyelitis caused by S. aureus, the NBD peptide serves a role in inhibiting osteolysis and promoting bone remodeling in the direction of osteogenesis. The effects were better than those produced by debridement alone, thus suggesting that it may have promising therapeutic potential in osteomyelitis.
骨髓炎的特征是进行性炎症性骨破坏和吸收，是一种难治性感染。金黄色葡萄球菌（S. aureus）是导致这种疾病的主要原因之一。这种致病微生物具有多种特性，使其易于参与骨髓炎的发生和发展。一种核因子（NF）-κB 必需调节剂结合域（NBD）肽，是一种细胞通透性的 IκB 激酶复合物抑制剂，已被报道可阻断破骨细胞生成，可能被认为是预防炎症性骨吸收的一种潜在策略。然而，NBD 肽是否可以调节金黄色葡萄球菌诱导的骨髓炎中的炎症和骨吸收仍有待确定。为了研究 NBD 在金黄色葡萄球菌诱导的骨髓炎中的作用，本研究获得了 NBD 肽，并证实其在体外抑制核因子κB 受体激活剂配体诱导的破骨细胞生成。随后，在实验动物的下颌骨中产生骨缺损并注射金黄色葡萄球菌，以建立体内骨髓炎模型。本研究分析了以下三个实验组：未处理组、清创处理组和清创处理加 NBD 肽给药组。结果显示，NBD 肽治疗以三维方式减少了骨缺损，并减少了骨吸收。据我们所知，本研究首次证明，在金黄色葡萄球菌引起的骨髓炎模型中，NBD 肽在抑制溶骨性和促进成骨方向的骨重塑方面发挥作用。其效果优于单独清创处理，提示其在骨髓炎中可能具有有前景的治疗潜力。
