Disease-Associated Particulates and Joint Inflammation; Mechanistic Insights and Potential Therapeutic Targets

Front Immunol. 2018 May 28:9:1145. doi: 10.3389/fimmu.2018.01145. eCollection 2018.

Abstract

It is now well established that intra-articular deposition of endogenous particulates, such as osteoarthritis-associated basic calcium phosphate crystals, gout-associated monosodium urate crystals, and calcium deposition disease-associated calcium pyrophosphate crystals, contributes to joint destruction through the production of cartilage-degrading enzymes and pro-inflammatory cytokines. Furthermore, exogenous wear-debris particles, generated from prosthetic implants, drive periprosthetic osteolysis which impacts on the longevity of total joint replacements. Over the last few years, significant insight has been gained into the mechanisms through which these particulates exert their effects. Not only has this increased our understanding of the pathological processes associated with crystal deposition but it has also led to the identification of a number of therapeutic targets to treat particulate-associated disease. In this review, we discuss recent developments regarding the cellular events triggered by joint-associated particulates, as well as future directions in therapy for particulate-related arthropathies.

Keywords: calcium deposition disease; gout; joint inflammation; osteoarthritis; particulates.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Arthritis / diagnosis
  • Arthritis / etiology*
  • Arthritis / metabolism*
  • Arthritis / therapy
  • Biomarkers
  • Calcium Pyrophosphate / adverse effects
  • Crystal Arthropathies / etiology
  • Crystal Arthropathies / metabolism
  • Crystal Arthropathies / pathology
  • Crystal Arthropathies / therapy
  • Disease Susceptibility*
  • Gene Expression Regulation
  • Humans
  • Molecular Targeted Therapy
  • Osteolysis
  • Particulate Matter / adverse effects*
  • Signal Transduction
  • Uric Acid / adverse effects

Substances

  • Biomarkers
  • Particulate Matter
  • Uric Acid
  • Calcium Pyrophosphate