Mammalian β-
defensins are small cationic
peptides of approximately 2-6 kDa that have been implicated in mediating innate immune defenses against microbial
infection. Previous studies have reported that mouse β-defensin-14 (MBD‑14), based on structural and functional similarities, appears to be an ortholog of human β-defensin-3 (HBD-3). The aim of this study was to identify the signaling pathways that contribute to the expression of MBD-14 in mouse osteoblasts (OBs) upon contact with methicillin-resistant Staphylococcus aureus (S. aureus) supernatant (SAS) to provide a theoretical basis for the use of MDB-14 as a therapeutic agent in the treatment of intramedullary
infection with S. aureus in vivo. The bacterial exoproducts released by S. aureus mainly include a large amount of
enterotoxins. Using mouse OBs, the release and regulation of MBD-14 was evaluated by real-time polymerase chain reaction (PCR) and enzyme‑linked
immunosorbent assay (ELISA) following exposure to SAS. The activation of the p38 mitogen‑activated
protein kinase (MAPK),
extracellular signal-regulated kinase (ERK) and nuclear factor-κB (NF-κB) pathways was determined by western blot analysis. OBs treated with
lipopolysaccharide (LPS) were used as the positive control. The results revealed that SAS significantly promoted the phosphorylation of
p38 MAPK, NF-κB and the inhibitory subunit of NF-κBα (IκBα) in a time-dependent manner. The treatment of OBs with
SB203580 (an inhibitor of
p38 MAPK) and
pyrrolidine dithiocarbamate (
PDTC, an inhibitor of NF-κB) prior to stimulation with SAS significantly inhibited the phosphorylation and
mRNA expression of
p38 MAPK and NF-κB p65, simultaneously reducing the release of MBD-14. Our findings suggest that the release of MBD-14 is mediated at least in part through the activation of
p38 MAPK and NF-κB in response to S. aureus‑secreted bacterial exoproducts. Moreover, our data demonstrate the innate immune capacity of OBs under conditions of bacterial challenge to enhance the local expression of this MBD-14, a
peptide with anti‑staphylococcal activity.