Extracellular matrix turnover and inflammation in chemically-induced TMJ arthritis mouse models

PLoS One. 2019 Oct 11;14(10):e0223244. doi: 10.1371/journal.pone.0223244. eCollection 2019.

Abstract

The temporomandibular joint (TMJ) is a fibrocartilaginous tissue critical for chewing and speaking. In patients with temporomandibular disorders (TMDs), permanent tissue loss can occur. Recapitulating the complexity of TMDs in animal models is difficult, yet critical for the advent of new therapies. Synovial fluid from diseased human samples revealed elevated levels of tumor necrosis factor alpha (TNF-alpha). Here, we propose to recapitulate these findings in mice by subjecting murine TMJs with TNF-alpha or CFA (Complete Freund's Adjuvant) in mandibular condyle explant cultures and by local delivery in vivo using TMJ intra-articular injections. Both TNF-alpha and CFA delivery to whole mandibular explants and in vivo increased extracellular matrix deposition and increased cartilage thickness, while TNF-alpha treated explants had increased expression of inflammatory cytokines and degradative enzymes. Moreover, the application of TNF-alpha or CFA in both models reduced cell number. CFA delivery in vivo caused soft tissue inflammation, including pannus formation. Our work provides two methods of chemically induced TMJ inflammatory arthritis through a condyle explant model and intra-articular injection model that replicate findings seen in synovial fluid of human patients, which can be used for further studies delineating the mechanisms underlying TMJ pathology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAMTS5 Protein / genetics
  • ADAMTS5 Protein / immunology
  • Adolescent
  • Adult
  • Aged
  • Animals
  • Arthritis, Experimental / chemically induced
  • Arthritis, Experimental / genetics
  • Arthritis, Experimental / immunology*
  • Cartilage, Articular / drug effects
  • Cartilage, Articular / immunology*
  • Cartilage, Articular / pathology
  • Collagen Type II / genetics
  • Collagen Type II / immunology
  • Collagen Type X / genetics
  • Collagen Type X / immunology
  • Disease Models, Animal
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / immunology*
  • Extracellular Matrix / pathology
  • Female
  • Freund's Adjuvant / administration & dosage
  • Gene Expression / drug effects
  • Gene Expression / immunology
  • Humans
  • Interleukins / genetics
  • Interleukins / immunology
  • Male
  • Mandibular Condyle / drug effects
  • Mandibular Condyle / immunology
  • Mandibular Condyle / pathology
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • Synovial Fluid / immunology
  • Temporomandibular Joint / drug effects
  • Temporomandibular Joint / immunology*
  • Temporomandibular Joint / pathology
  • Temporomandibular Joint Disorders / genetics
  • Temporomandibular Joint Disorders / immunology*
  • Temporomandibular Joint Disorders / pathology
  • Tissue Culture Techniques
  • Tumor Necrosis Factor-alpha / administration & dosage

Substances

  • Col10a1 protein, mouse
  • Col2a1 protein, mouse
  • Collagen Type II
  • Collagen Type X
  • Interleukins
  • Tumor Necrosis Factor-alpha
  • Freund's Adjuvant
  • ADAMTS5 Protein
  • Adamts5 protein, mouse