Since both conventional (antimicrobial) and non-antimicrobial tetracyclines inhibited periodontal bone resorption induced by endotoxin injection, MMP-mediated bone loss in this model can be prevented by inhibition of MMPs.

Temporomandibular joint dysfunction has been observed in patients with systemic polyarthritis (rheumatoid or psoriatic). Rats with systemic adjuvant arthritis (AA) also develop temporomandibular joint pathology. Collagenase and gelatinase are matrix metalloproteinases (MMPs) involved in the destruction of arthritic joints.' Published reports indicate that tetracyclines including their nonantimicrobial analogs (CMTs) can inhibit MMPs and prevent tissue destruction during various diseases.* Recently, Ramamurthy et aL4 reported that the administration of a combination of CMT + NSAID (Tenidap [TD]) to arthritic rats inhibited bone resorption more than did either drug alone because NSAID therapy increased CMT uptake in the diseased joints possibly by reducing inflammatory stasis. In the current study, we determined the effect of CMT-1 /TD combination therapy on the amelioration of temporomandibular joint pathology. Male Lewis rats (150 g of body weight) were made arthritic by injecting Freund's adjuvant at the base of the tail. The rats were then distributed into the following groups: normal, untreated AA, AA + TD (2 mg/rat), AA + CMT-1 (4 mg/rat), and AA + TD + CMT-1 (Combo). All drugs were suspended in 2% carboxymethylcellulose and administered by oral gavage once a day for 23 days. The rats became arthritic by day 13.At the termination of the experiments (day 21), some rat heads were fixed in formalin for histologic and X-ray examination. Other specimens were frozen for later measurement of MMP levels in extracts of the temporomandibular joint. The jaws were x-rayed using mammography x-ray film. Histologic study of the temporomandibular joint was carried out on serial sections stained with hematoxylin and eosin. Both collagenase and gelatinase were determined after dissecting the intact frozen temporomandibular joint. Matrix metalloproteinases were extracted from pooled tissues3 and assayed for collagenase (using ['H-methyl] collagen as substrate) by SDS-PAGE/ fluorography and for gelatinase by zymography.X-ray analysis showed increased temporomandibular joint destruction in AA rats

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