Endosomal damage and TLR2 mediated inflammasome activation by alkane particles in the generation of aseptic osteolysis

Radhashree Maitra, Cristina C. Clement, Brian Scharf, Giovanna M. Crisi, Sriram Chitta, Daniel Paget, P. Edward Purdue, Neil Cobelli, Laura Santambrogio

Research output: Contribution to journalReview articlepeer-review

70 Scopus citations

Abstract

Ultra-high molecular weight polyethylene is widely used as a bearing surface in prosthetic arthroplasty. Over time the generation of implant-derived wear particles can initiate an inflammatory reaction characterized by periprosthetic inflammation and ultimately bone resorption at the prosthetic bone interface. Herein we present evidence that the different sized particles as well as the different length alkane polymers generated by implant wear leads to a two component inflammatory response. Polymeric alkane structures, with side chain oxidations, directly bind and activate the TLR-1/2 signaling pathway. Whereas micron- and nanometer-sized particulate debris are extensively phagocyted and induce enlargement, fusion and disruption of endosomal compartments. The resulting lysosomal damage and subsequent enzymatic leakage induces the NALP3 inflammasome activation as determined by cathepsins S and B cytosolic release, Caspase 1 activation and processing of pro-IL-1β, and pro-IL-18. These two processes synergistically results in the initiation of a strong inflammatory response with consequent cellular necrosis and extracellular matrix degradation.

Original languageEnglish (US)
Pages (from-to)175-184
Number of pages10
JournalMolecular Immunology
Volume47
Issue number2-3
DOIs
StatePublished - Dec 1 2009

Keywords

  • Aseptic osteolysis
  • Endosomal damage
  • Inflammation
  • UHMWPE

ASJC Scopus subject areas

  • Immunology
  • Molecular Biology

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