| Osteomyelitis refers to a type of inflammatory disease caused by direct invasion into the bone by exogenous pathogen or infection originated from other tissue.Its main feature is the persistent inflammation and bone destruction.As one of the dominant subtype,due to the specific pathogenesis of traumatic osteomyelitis,external infectious factors can directly invade our organism and directly damage the homeostasis of the bone.Traumatic osteomyelitis induces overexpression of local inflammation,which can cause ischemic necrosis and form sequestered bones.Moreover,it can induce the formation of bacterial biofilms,leading to a series of problems such as prolonged course of disease,higher risk of complications,and higher recurrence rate.It has brought great burden to both doctors and patients and social resources.As the most important part of the body's defense against infection,the body's immunity is closely related to the pathogenesis of traumatic osteomyelitis,especially the internal mechanism of immunity regulated by pathogens,which may point out a novel direction for the clinical treatment of osteomyelitis.This study focuses on these following aspects:the correlation between vitamin D and traumatic osteomyelitis,vitamin D receptors regulate macrophage phagocytosis and bactericidal,and vitamin D/vitamin D receptor pathways involved in regulating Staphylococcus aureus-mediated macrophage apoptosis,the exploration of the mechanism of apoptosis and the up-regulation of VDR expression reducing the severity of traumatic osteomyelitis by inhibiting the apoptosis of macrophages.Through clinical data collection,we compared the levels of vitamin D,TNF-?and VDR protein expression in patients with clinical traumatic osteomyelitis and patients with normal healing after internal fixation of fractures,and assessed the correlation between vitamin D levels in the body and the morbidity of traumatic osteomyelitis.In the in vitro experiment,the phagocytosis and bactericidal function of macrophages was measured first;then the expression of NF-?B and the expression of apoptosis markers such as Fas,Bax,Bcl-2,and Caspase-3 of macrophages were detected.In addition,we detected the count of macrophages at different stage of apoptosis;Through the detection of the downstream mechanism of VDR,we continue to explore the deep mechanism of VDR inhibiting macrophage apoptosis.Finally,we established a mouse model of femoral traumatic osteomyelitis to verify that vitamin D participates in the regulation of macrophage apoptosis.Based on the above research results,clinical data analysis shows that the expression of vitamin D and vitamin D receptors in the body are correlated with the pathogenesis of traumatic osteomyelitis.In vitro experiments confirmed that vitamin D stimulation can enhance the phagocytosis and bactericidal function of macrophages.This phenomenon is caused by the high expression of vitamin D receptors to inhibit the activation of NF-?B into the nucleus,and activate the downstream A20 to exert a synergistic inhibitory effect,and then down-regulate subsequent TNF-? expression achieves anti-inflammatory and anti-apoptotic functions.Subsequent in vivo experiments established a mouse model of traumatic osteomyelitis in the femur,verifying that vitamin D stimulation can reduce peripheral blood TNF-? levels,inhibit macrophage apoptosis and reduce the severity of traumatic osteomyelitis.Our research shows that traumatic osteomyelitis is related to the level of vitamin D in the host.Vitamin D can stimulate the up-regulation of vitamin D receptor expression and promote the phagocytosis and bactericidal function of macrophages;up-regulation of vitamin D receptor expression can inhibit NF-?B It stimulates the up-regulation of downstream A20 expression and exerts a synergistic inhibitory effect on NF-?B activation.Under TNF-? stimulation,A20 continues to exert a negative feedback effect to inhibit NF-?B transcription and complete the mediation of Staphylococcus aureus Inhibition of the apoptotic pathway of macrophages. |
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