Matrix metalloproteinases in mild and severe temporomandibular joint internal derangement synovial fluid

Abstract

Objectives: The first objective of this study was to verify the presence of and identify the molecular forms of matrix metalloproteinases (MMPs), including collagenases (MMP-1, MMP-8, and MMP-13) and gelatinases (MMP-2 and MMP-9), in the synovial fluid (SF) of mild and severe temporomandibular joint internal derangement (TMJ-ID). Another objective was to evaluate whether the SF MMPs are potential diagnostic markers that reflect the stage of intra-articular inflammation in the TMJ.

Study design: The subjects were 44 patients with mild (n = 16) or severe (n = 28) TMJ-ID; they were classified on the basis of subjective symptoms, clinical and radiographic findings, and surgical observations. The patients were surgically treated, and SF samples were collected immediately before the operation. The collagenase activity of SF samples was analyzed by means of a type I collagen degradation assay. The levels and molecular forms of the SF MMPs as well as the tissue inhibitors of MMPs (TIMP-1 and TIMP-2) were analyzed with Western immunoblotting and gelatin zymography.

Results: The SF of both the mild and the severe TMJ-ID patients exhibited free collagenase activity and activity capable of further degrading the (3/4)(alphaA) fragments. Ninety-two-kilodalton proMMP-9 and its 121-kD complex form, as well as 72-kD proMMP-2 were significantly increased in the mild TMJ-ID group (P <.05 in all cases). Both 70- to 80-kD neutrophil type and 45- to 55-kD mesenchymal cell-type MMP-8 (corresponding to the latent and active forms) were observed in mild and severe TMJ-ID SF, but they predominated in mild TMJ-ID. Both MMP-1 and MMP-13 were observed in both groups, and in mild TMJ-ID SF the low-molecular weight forms of MMP-1 indicated activation of the enzyme.

Conclusions: The degradation of type I collagen in the TMJ is evidently due to the collective action of many collagenolytic MMPs present in the SF of patients with mild and severe TMJ-ID. The elevated levels of MMP-2, MMP-9, and MMP-8 in the SF of patients with mild TMJ-ID eventually reflect the active phase of TMJ destruction. These observations may have considerable diagnostic and therapeutic significance in the management of TMJ disorders.