Gene expression of MMP-3 and TIMP-2 in the TMJ of mice with osteoarthritis

Abstract

Osteoarthritis (OA) is a chronic disease that causes degeneration and loss of articular cartilage. Because the relative balance of matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) is thought to trigger OA, even slight deviations in gene expression can contribute to its progression. However, molecular biological techniques have not yet been able to demonstrate the relationship of OA with MMP-3 and TIMP-2 in the temporomandibular joint (TMJ). We used these techniques to investigate the expression pattern of MMP-3 and TIMP-2 during disease progression in the TMJ of male Institute for Cancer Research (ICR) mice, which are models for osteoarthritis. In addition, we observed the ets-1 gene, which is a transcription factor of MMP-3. The expression of MMP-3, TIMP-2 and ets-1 in the TMJ of ICR mice was examined using reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time PCR. TIMP-2 disappeared in the cartilage as the disease developed, while MMP-3 and ets-1 increased. In contrast, RT-PCR and real-time PCR showed that levels of MMP-3, TIMP-2 and ets-1 increased in the synovium and disc. These results suggest that the balance between MMP-3 and TIMP-2 is disrupted in the osteoarthritic cartilage, and that this may trigger progressive osteoarthritis. Ets-1 expression may also play an important role in development of OA.