Progression of cartilage degradation, bone resorption and pain in rat temporomandibular joint osteoarthritis induced by injection of iodoacetate

PLoS One. 2012;7(9):e45036. doi: 10.1371/journal.pone.0045036. Epub 2012 Sep 11.

Abstract

Background: Osteoarthritis (OA) is an important subtype of temporomandibular disorders. A simple and reproducible animal model that mimics the histopathologic changes, both in the cartilage and subchondral bone, and clinical symptoms of temporomandibular joint osteoarthritis (TMJOA) would help in our understanding of its process and underlying mechanism.

Objective: To explore whether injection of monosodium iodoacetate (MIA) into the upper compartment of rat TMJ could induce OA-like lesions.

Methods: Female rats were injected with varied doses of MIA into the upper compartment and observed for up to 12 weeks. Histologic, radiographic, behavioral, and molecular changes in the TMJ were evaluated by light and electron microscopy, MicroCT scanning, head withdrawal threshold test, real-time PCR, immunohistochemistry, and TUNEL assay.

Results: The intermediate zone of the disc loosened by 1 day post-MIA injection and thinned thereafter. Injection of an MIA dose of 0.5 mg or higher induced typical OA-like lesions in the TMJ within 4 weeks. Condylar destruction presented in a time-dependent manner, including chondrocyte apoptosis in the early stages, subsequent cartilage matrix disorganization and subchondral bone erosion, fibrosis, subchondral bone sclerosis, and osteophyte formation in the late stages. Nociceptive responses increased in the early stages, corresponding to severe synovitis. Furthermore, chondrocyte apoptosis and an imbalance between anabolism and catabolism of cartilage and subchondral bone might account for the condylar destruction.

Conclusions: Multi-level data demonstrated a reliable and convenient rat model of TMJOA could be induced by MIA injection into the upper compartment. The model might facilitate TMJOA related researches.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkylating Agents / administration & dosage
  • Alkylating Agents / toxicity
  • Animals
  • Apoptosis / drug effects
  • Arthralgia / chemically induced*
  • Bone Resorption / chemically induced*
  • Cartilage, Articular / drug effects*
  • Cartilage, Articular / metabolism
  • Cartilage, Articular / pathology
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Chondrocytes / drug effects
  • Chondrocytes / metabolism
  • Chondrocytes / pathology
  • Disease Models, Animal
  • Disease Progression
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Immunohistochemistry
  • Injections
  • Iodoacetates / administration & dosage
  • Iodoacetates / toxicity*
  • Matrix Metalloproteinase 3 / genetics
  • Matrix Metalloproteinase 3 / metabolism
  • Microscopy, Electron
  • Osteoarthritis / chemically induced*
  • Rats
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction
  • Temporomandibular Joint / drug effects*
  • Temporomandibular Joint / pathology
  • Temporomandibular Joint / ultrastructure
  • Time Factors
  • X-Ray Microtomography

Substances

  • Alkylating Agents
  • Iodoacetates
  • Caspase 3
  • Matrix Metalloproteinase 3

Grants and funding

This project is supported by the National Natural Science Foundation of China (Grant No. 81070849) and China International Science and Technology Cooperation (Grant No. 2010DFB32980). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.