The Potential Role of Increasing the Release of Mouse β- Defensin-14 in the Treatment of Osteomyelitis in Mice: A Primary Study

Abstract

Mammalian β-defensins are small cationic peptides that have been implicated in mediating innate immune defenses against microbial infection. Mouse β-defensin-14 (MBD-14), based on structural and functional similarities, appears to be an ortholog of human β-defensin-3 (HBD-3). Previous studies identified signaling pathway p38 mitogen-activated protein kinase (MAPK) that contributed to the expression of MBD-14 in mouse osteoblasts upon contacted with methicillin-resistance Staphylococcus aureus (MRSA) supernatant, which provided a theoretical basis as a promising therapeutic target in the treatment of intramedullary infection with MRSA in vivo. In this study, the medullary cavities of tibiae were contaminated with MRSA 103 colony forming units and different doses of p38 MAPK agonists anisomycin were followed as group III or IV in 30 mice. Fifteen animals that received phosphate- buffered saline served as group II and 15 mice were not contaminated with MRSA and received phosphate-buffered saline served as controls (group I). Follow-up was 7 days. In day 1, day 4 and day 7 postoperatively, infection was evaluated by blood routine, microbiological and histological analyses after sacrifice. All animals of group II developed microbiological and histological signs of infection. Histological signs of infection, white blood counts and cultures of group III and IV showed significantly reduced bacterial growth compared to cultures of group II. Simultaneously, different doses of anisomycin significantly induced the expression of osteoblast-associated genes, including alkaline phosphatase, osteocalcin and collagen type I. In addition, the expression of HBD-3 in human interfacial membranes around infected periprosthetic joint by staphylococcus contaminated was evaluated, and the expression pattern changed with significant induction of HBD-3 in infected periprosthetic joint compared with aseptic loosening under inflammatory conditions. Our primary study indicated that the potential antibacterial role of increased MBD-14 in the osteomyelitis mouse model.

Ultrasound microbubbles enhance human β-defensin 3 against biofilms

“…Our recent studies identified that when mouse osteoblasts contacted with MRSA supernatant, the relevant activated signaling pathway p38 mitogen-activated protein kinase could contribute to the obvious release of MBD-14, which is the structural and functional ortholog of HBD-3 [43,44]. Meanwhile, we also indicated the potential role of increasing the release of MBD-14 in the treatment of osteomyelitis in mice [22,45]. In addition to their role of local high Fig.…”

“…Animals were prepared for surgery as follows: the back of the mice was shaved, depilated, and disinfected with alcohol. To provide sterile conditions during surgery, animals were placed on sterile drapes and bodies were covered with sterile sheets [22]. Subsequently, two biofilm-infected titanium plates, which had been gently washed thrice with PBS to remove nonadherent bacteria, were implanted subcutaneously bilateral to the spine, as reported previously, with one plate on each side [8] (Fig.…”

Therapeutics and delivery vehicles for local treatment of osteomyelitis

“…66 In one interesting study, a murine model for the study of human levels. 55 In a following study, infections in mice treated with HBD-3…”

“…Antimicrobial peptides (AMPs), found naturally within human neutrophils and in epithelial secretions, have gained popularity in recent years as therapeutics for osteomyelitis. 53 The list of AMPs is extensive, 54 but some investigated for S. aureus clearance include: β-defensins, 55,56 Magainin 2 (also known by its analog, pexiganan acetate), 57,58 human lactoferrin 1-11 (hLF1-11), 59,60 isolates of bee venom, [61][62][63][64] snake venom, 65 and L-homocarnosine. 66 In one interesting study, a murine model for the study of human levels.…”

The mechanism of human β-defensin 3 in MRSA-induced infection of implant drug-resistant bacteria biofilm in the mouse tibial bone marrow

“…The expression levels of IL-10, TNF-α, IL-1α and IP-10 in the model group at each time-point were significantly higher than the other two groups, and the difference was statistically significant; in terms of the comparison between the HBD-3 group and vancomycin group, the difference was not statistically significant. It was suggested that HBD-3 and vancomycin could significantly reduce the IL-10, TNF-α, IL-1α and IP-10 mediated inflammatory response (14). In conclusion, β-defensin 3 can inhibit the bacterial growth by regulating inflammation and immune response in MRSA-induced implant drug-resistant bacteria biofilm infection in mouse tibial bone marrow.…”