Inhibition of pyroptosis attenuates Staphylococcus aureus-induced bone injury in traumatic osteomyelitis

Background:Osteomyelitis is a severe bone infection and typically leads to progressive bone resorption, destruction and dysfunction. Pyroptosis is a form of programmed cell death involved in various infectious diseases. However, the identification of pyroptosis and the role it plays in osteomyelitis remains to be clarified. In this study, we investigated the expression of pyroptosis-associated proteins in osteomyelitis and the effects of inhibiting pyroptosis on S. aureus-induced osteomyelitis both in vitro and in vivo.

Methods:The expression of pyroptosis-associated protein-NLRP3 (NLR Family Pyrin Domain Containing 3), Caspase1 and GSDMD (GasderminD) were examined in murine and human infectious bone fragments by western blot. Bone destruction was evaluated by microcomputed tomography (µCT). The concentration of inflammatory factors was tested by Enzyme linked Immunosorbent Assay (ELISA). The expression of pyroptosis-associated gene was detected by real-time quantitative polymerase chain reaction (RT-qPCR).

Results:The expression of pyroptosis-associated proteins in infectious bone fragments from patients with osteomyelitis was significantly higher than uninfected bone. Additionally, in S. aureus-induced murine osteomyelitis model, higher expression of pyroptosis-associated proteins was noticed. Furthermore, the inhibitors of pyroptosis-associated proteins alleviated S. aureus-induced pyroptosis both in vivo and in vitro. More importantly, the inhibition of pyroptosis restored the bone formative property, attenuated the aberrant activation of osteoclast in vitro and reversed bone injury in vivo.

Conclusions:Our study identified pyroptosis as a key pathway in osteomyelitis and elaborated that the inhibition of pyroptosis could attenuate S. aureus-induced bone destruction in osteomyelitis, providing a potential treatment target to osteomyelitis.

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