Open AccessInhibition of PAD4 mediated neutrophil extracellular traps prevents fibrotic osseointegration failure in a tibial implant murine model
Author(s) -
Emile-Victor Kuyl,
Fei Shu,
Branden Sosa,
Juan de Dios Barajas López,
Di Qin,
Tania Pannellini,
Lionel B. Ivashkiv,
Matthew B. Greenblatt,
Mathias P. Bostrom,
Xu Yang
Publication year - 2021
Publication title -
the bone and joint journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.587
H-Index - 181
eISSN - 2049-4408
pISSN - 2049-4394
DOI - 10.1302/0301-620x.103b7.bjj-2020-2483.r1
Subject(s) - osseointegration , implant , neutrophil extracellular traps , implant failure , inflammation , immune system , innate immune system , extracellular matrix , medicine , immunology , microbiology and biotechnology , surgery , biology
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.