Expression and localization of MMP-3 and TIMP-2 in the temporomandibular joint of osteoarthritic mice

  • Sako Jun
    Graduate School of Dentistry(Oral and Maxillofacial Surgery), Osaka Dental University

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Male Institute for Cancer Research(ICR)mice are models for osteoarthritis. I used histological and immunohistochemical methods, and enzymography to investigate the expression and localization of MMP-3 and TIMP-2 in the temporomandibular joint (TMJ)of these mice as the disease progressed. Haematoxylin and eosin staining showed progressive cartilage damage, and toluidine blue staining indicated proteoglycan loss as the mice aged. Immunohistochemistry revealed that MMP-3 staining was maintained as the disease progressed, while TIMP-2 staining decreased. During late stages of the disease, MMP-3+ cells were located in damaged areas of the cartilage. Immunoblotting studies also showed that TIMP-2 in the cartilage disappeared as the disease developed, while MMP-3 increased. In contrast, in the synovium, levels of both MMP-3 and TIMP-2 increased as shown by both immunohistochemistry and immunoblotting.<br> These observations suggest that the balance between MMP-3 and TIMP-2 is disrupted in the surface layer of the osteoarthritic cartilage, and that this may trigger progressive osteoarthritis. The scenario in the synovium suggests that the synovium may participate later in the disease by being an additional source of MMPs. In addition, this study corroborates previous work suggesting that TIMP-2 may act to inhibit MMP-3, since the antibodies specific for each molecule can both bind a band that most likely represents a complex of the two proteins. Immunohistochemical work also showed that MMP-3 and TIMP-2 were present in the same cells.

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