Psychological Stress Alters Extracellular Matrix Metabolism in Mandibular Condylar Cartilage

Chin J Dent Res. 2017;20(3):125-135. doi: 10.3290/j.cjdr.a38767.

Abstract

Objective: To explore the effect of long-term stress on the temporomandibular joint (TMJ) condyle and its possible underlying mechanism.

Methods: A 12-week, chronic unpredictable mild stress (CUMS) model was used to induce long-term psychological stress in rats. Rats were randomly divided into control group (CONT), chronic unpredictable mild stress group (CUMS) and chronic unpredictable mild stress with fluoxetine treatment group (CUMS + DT) (n = 30 per group). A 5 mg/kg dose of fluoxetine was intraperitoneally injected daily 0.5 h before stress. A sucrose preference test, plasma corticosterone test and open-field test were performed to verify the feasibility of the CUMS model. Histopathology was used to observe the pathological changes of condyle. The expression levels of inflammatory cytokines, matrix metalloproteases (MMPs) and extracellular matrix (ECM) were measured by real-time polymerase chain reaction, western blotting and immunohistochemistry.

Results: At 8 and 12 weeks after exposure to CUMS, the rats showed higher plasma corticosterone than the control rats. Additionally, for the open-field test, the rats exposed to CUMS spent more time in the centre zone and moved a shorter distance than the control and drug treatment rats. In addition, pathological changes in the condylar cartilage occurred in the 8-week CUMS subgroup and were more obvious in the 12-week CUMS subgroup. The CUMS caused an increase in the secretion of inflammatory cytokines, imbalanced expression of MMPs and tissue inhibitor of metalloproteinase-1 and accelerated degradation of ECM in condylar cartilage in a time-dependent manner.

Conclusion: Osteoarthritis-like lesions can be caused by long-term CUMS in the mandibular condyles, which suggests that the imbalance in chondrocyte-secreted regulatory factors within the cartilage of the TMJ may play an important role in cartilage injury induced by psychological stress.

MeSH terms

  • Aggrecans / drug effects
  • Aggrecans / genetics
  • Aggrecans / metabolism
  • Animals
  • Behavior, Animal
  • Blotting, Western
  • Cartilage, Articular / drug effects
  • Cartilage, Articular / metabolism*
  • Collagen Type II / drug effects
  • Collagen Type II / genetics
  • Collagen Type II / metabolism
  • Corticosterone / metabolism
  • Cytokines / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / metabolism*
  • Fluoxetine / pharmacology
  • Immunohistochemistry
  • Male
  • Mandibular Condyle / drug effects
  • Mandibular Condyle / metabolism*
  • Matrix Metalloproteinase 3 / drug effects
  • Matrix Metalloproteinase 3 / genetics
  • Matrix Metalloproteinase 3 / metabolism
  • Matrix Metalloproteinase 9 / drug effects
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • RNA, Messenger / drug effects
  • RNA, Messenger / metabolism
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Real-Time Polymerase Chain Reaction
  • Selective Serotonin Reuptake Inhibitors / pharmacology
  • Stress, Psychological / genetics
  • Stress, Psychological / metabolism*
  • Temporomandibular Joint
  • Tissue Inhibitor of Metalloproteinase-1 / drug effects
  • Tissue Inhibitor of Metalloproteinase-1 / genetics
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism

Substances

  • Aggrecans
  • Collagen Type II
  • Cytokines
  • RNA, Messenger
  • Serotonin Uptake Inhibitors
  • TIMP1 protein, rat
  • Tissue Inhibitor of Metalloproteinase-1
  • Fluoxetine
  • Matrix Metalloproteinase 3
  • Matrix Metalloproteinase 9
  • Mmp9 protein, rat
  • Corticosterone