The inhibition of microRNA-203 on ischemic reperfusion injury after total knee arthroplasty via suppressing MYD88-mdiated toll-like receptor signaling pathway

Abstract

Ischemia reperfusion injury (IRI), a complex phenomenon often encountered in surgery, can lead to local and distant tissue destruction and sometimes even death. microRNA-203 (miR-203) has been reported to negatively regulate ischemia induced microglia activation with a feedback to myeloid differentiation primary-response gene 88 (MYD88). Accordingly, our study is to verify the effect of miR-203 and MYD88 on mice in IRI after total knee arthroplasty (TKA). After establishment of IRI mouse model, heart rate (HR) and mean arterial pressure (MAP) in mice were determined. The functional role of miR-203 in IRI was determined using ectopic expression, knockdown and reporter assay experiments. Levels of interferon γ (IFN-γ), interleukin 10 (IL-10), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), creatine kinase (CK), lactate dehydrogenase (LDH), superoxide dismutase (SOD) and malondialdehyde (MDA) were detected, and expression of miR-203, MYD88, toll-like receptor 4 (TLR4), Faslg, Cleaved-Caspase-3, B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) was evaluated. Initially, HR and MAP were decreased in IRI mice. Forced expression of miR-203 and silencing of MYD88 increased levels of SOD and IL-10 but decreased levels of MDA, CK, LDH, TNF-α, IL-6 and IFN-γ. Additionally, forced expression of miR-203 and silencing of MYD88 increased Bcl-2 expression but decreased MYD88, TLR4, Cleaved-Caspase-3, Falsg and Bax expression. MYD88, a target gene of miR-203, was decreased following miR-203 promotion, while the TLR signaling pathway inactivation occurred following MYD88 silencing. Generally, our study demonstrated the protective effects of miR-203 on mice with IRI after TKA through inhibiting TLR signaling pathway by negatively regulating MYD88.