Osteoarthritis-like damage of cartilage in the temporomandibular joints in mice with autoimmune inflammatory arthritis.
OBJECTIVE
To study temporomandibular joint (TMJ) involvement in an autoimmune murine model of rheumatoid arthritis (RA), a disease characterized by inflammatory destruction of the synovial joints. Although TMJ dysfunction is frequently found in RA, TMJ involvement in RA remains unclear, and TMJ pathology has not been studied in systemic autoimmune animal models of RA.


METHODS
Proteoglycan (PG) aggrecan-induced arthritis (PGIA) was generated in genetically susceptible BALB/c mice. TMJs and joint tissues/cartilage were harvested for histological and immunohistochemical analyses and RNA isolation for quantitative polymerase chain-reaction. Serum cytokine levels were measured in mice with acute or chronic arthritis, and in non-arthritic control animals.


RESULTS
Despite the development of destructive synovitis in the limbs, little or no synovial inflammation was found in the TMJs of mice with PGIA. However, the TMJs of arthritic mice showed evidence of aggrecanase- and matrix metalloproteinase-mediated loss of glycosaminoglycan-containing aggrecan, and in the most severe cases, structural damage of cartilage. Serum levels of pro-inflammatory cytokines, including interleukin (IL)-1β, were elevated in arthritic animals. Expression of the IL-1β gene was also high in the inflamed limbs, but essentially normal in the TMJs. Local expression of genes encoding matrix-degrading enzymes (aggrecanases and stromelysin) was upregulated to a similar degree in both the limbs and the TMJs.


CONCLUSIONS
We propose that constantly elevated levels of catabolic cytokines, such as IL-1β, in the circulation (released from inflamed joints) create a pro-inflammatory milieu within the TMJ, causing local upregulation of proteolytic enzymes and subsequent loss of aggrecan from cartilage.
Section of Molecular Medicine, Department of Orthopedic Surgery, Rush University Medical Center, Chicago, IL 60612, USA.
S
S
Ghassemi-Nejad
T
T
Kobezda
T A
TA
Rauch
C
C
Matesz
T T
TT
Glant
K
K
Mikecz
D000818:Animals; D001172:Arthritis, Rheumatoid; D002358:Cartilage, Articular; D002908:Chronic Disease; D016207:Cytokines / Q000097:blood*; D004195:Disease Models, Animal; D010450:Endopeptidases / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism; D007150:Immunohistochemistry; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010003:Osteoarthritis; D013583:Synovial Membrane / Q000473:pathology; D013704:Temporomandibular Joint / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation
D016207:Cytokines; D006025:Glycosaminoglycans; D010450:Endopeptidases; D019278:Matrix Metalloproteinase 3; C083641:aggrecanase
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