Degradative pathways in tissues of the temporomandibular joint - Use of invitro and in vivo models to characterize matrix metalloproteinase and cytokine activity

Identification of a small animal model that undergoes pathological temporom andibular joint (TMJ) degeneration would represent a significant research t ool. To date however, no such model has been described. We therefore have i nvestigated the pathological and immunohistochemical features of the TMJ of a transgenic mouse that over expresses the human form of TNF alpha. The TM J of this animal appears to undergo changes that resemble arthriditics of t emporomandibular dysfunction. Furthermore, the disc and articular cells exp ress MMP9 and IL-l. Future work should validate this animal model as one th at would have utility for the study of TMJ disorders. Maintenance of connec tive tissues in joints such as the TMJ is a normal process that allows for the reconstitution of important anatomic features. This maintenance involve s both the removal and re-synthesis of structural proteins such as collagen s, elastins and proteoglycans. An imbalance in the pathways for degradation and synthesis can lead to the degeneration of joint tissues. We describe t he presence of a matrix metalloproteinase. MMP9 (92-kD gelatinase), in TMJ disc and articular cells that likely function in the degradative process. A dditionally, we show that this enzyme is under the control of pro-inflammat ory cytokines whereby TGF beta and IL-l stimulate and PGE(2) inhibits its a ctivity. Copyright (C) 2001 S. Karger AG, Basel.