Osteoarthritis-like damage of cartilage in the temporomandibular joints in mice with autoimmune inflammatory arthritis

Abstract

Summary 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. Conclusion 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.

Comparative study on serum‐induced arthritis in the temporomandibular and limb joint of mice

“…On the other hand, the proteoglycan (PG) aggrecan‐induced arthritis (PGIA) model described by Ghassemi‐Nejad et al is an autoimmune arthritis model . The authors compared the limb joints to the TMJ and observed that although destructive synovitis occurred in the limbs, there were no histological and immunohistochemical signs of inflammation in the TMJ, hence confirming our findings.…”

“…The authors compared the limb joints to the TMJ and observed that although destructive synovitis occurred in the limbs, there were no histological and immunohistochemical signs of inflammation in the TMJ, hence confirming our findings. Only in severe cases of arthritis, structural damages were seen in the TMJ . However, although these results are similar to ours, the evaluation of the TMJ was performed at days 49 and 50, thus at a more advanced RA stage .…”

“…Only in severe cases of arthritis, structural damages were seen in the TMJ . However, although these results are similar to ours, the evaluation of the TMJ was performed at days 49 and 50, thus at a more advanced RA stage . Moreover, the signs of destruction became even more evident after the mice reached late chronic phases compared to earlier stages.…”

Osteoarthritis in temporomandibular joint of Col2a1 mutant mice

“…Research on TMJ OA involving animal models is still developing (2, 10–14). Currently, TMJ disorder diagnoses are based on non-specific symptoms.…”

“…An OA animal model is an important tool in understanding TMJ disease (2, 10, 15, 18). Human studies can only describe TMJ OA, whereas animal models may elucidate a cause and effect relationship that might allow for TMJ disease reversal and a universal understanding of TMJ OA pathobiochemistry that is not currently available (14).…”