骨整合
植入
中性粒细胞胞外陷阱
植入物失效
先天免疫系统
免疫系统
医学
炎症
体内
免疫学
外科
作者
Emile-Victor Kuyl,Fei Shu,Branden Sosa,Juan D. Lopez,Di Qin,Tania Pannellini,Lionel B. Ivashkiv,Matthew B. Greenblatt,Mathias P.G. Bostrom,Xu Yang
出处
期刊:The bone & joint journal
[British Editorial Society of Bone and Joint Surgery]
日期:2021-07-01
卷期号:103-B (7 Supple B): 135-144
被引量:2
标识
DOI:10.1302/0301-620x.103b7.bjj-2020-2483.r1
摘要
Aims Aseptic loosening is a leading cause of uncemented arthroplasty failure, often accompanied by fibrotic tissue at the bone-implant interface. A biological target, neutrophil extracellular traps (NETs), was investigated as a crucial connection between the innate immune system’s response to injury, fibrotic tissue development, and proper bone healing. Prevalence of NETs in peri-implant fibrotic tissue from aseptic loosening patients was assessed. A murine model of osseointegration failure was used to test the hypothesis that inhibition (through Pad4 -/- mice that display defects in peptidyl arginine deiminase 4 (PAD4), an essential protein required for NETs) or resolution (via DNase 1 treatment, an enzyme that degrades the cytotoxic DNA matrix) of NETs can prevent osseointegration failure and formation of peri-implant fibrotic tissue. Methods Patient peri-implant fibrotic tissue was analyzed for NETs biomarkers. To enhance osseointegration in loose implant conditions, an innate immune system pathway (NETs) was either inhibited ( Pad4 -/- mice) or resolved with a pharmacological agent (DNase 1) in a murine model of osseointegration failure. Results NETs biomarkers were identified in peri-implant fibrotic tissue collected from aseptic loosening patients and at the bone-implant interface in a murine model of osseointegration failure. Inhibition ( Pad4 -/- ) or resolution (DNase 1) of NETs improved osseointegration and reduced fibrotic tissue despite loose implant conditions in mice. Conclusion This study identifies a biological target (NETs) for potential noninvasive treatments of aseptic loosening by discovering a novel connection between the innate immune system and post-injury bone remodelling caused by implant loosening. By inhibiting or resolving NETs in an osseointegration failure murine model, fibrotic tissue encapsulation around an implant is reduced and osseointegration is enhanced, despite loose implant conditions. Cite this article: Bone Joint J 2021;103-B(7 Supple B):135–144.
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