Urokinase and its receptor in follicular and inflammatory cysts of the jaws.

OBJECTIVE: Proteases are considered critical in peri-cystic tissue degradation required in jaw cyst expansion. We studied the expression of the plasminogen activation system (plasminogen activators; their inhibitor type-1, PAI-1; the receptor for the urokinase-type plasminogen activator, uPAR) in follicular and inflammatory cysts of the jaw, to identify a possible role of this system in jaw cyst enlargement. MATERIALS AND METHODS: Jaw cysts were collected by therapeutic enucleation. ELISA and casein zymography were used to measure and characterize plasminogen activators in cyst fluid. By immunohistochemistry we examined the presence of uPAR in cyst walls and inflammatory cells, and by Western blotting the molecular forms of uPAR within the cyst fluid. RESULTS: Inflammatory cysts fluid contained higher amounts of plasminogen activators of the urinary-type (uPA), and lower amounts of PAI-1, when compared to follicular cysts fluid. Epithelial layers of both types of cysts and inflammatory cells expressed uPAR. Native 3-domain uPAR was scarcely detectable within cysts, where its cleavage was accounted for by uPA. CONCLUSION: These data suggest a plasminogen activation-dependent mechanism of cyst enlargement, where only the outward uPAR expressed on epithelial cells and on inflammatory cells direct the peri-cystic protease cascade, in a way similar to tumor enlargement within tissues.

Inhibition of matrix metalloproteinase-1 by dichloromethylene bisphosphonate (clodronate).

Interstitial collagenase present in human jaw cyst extract and purified human fibroblast-type collagenase (MMP-1) were both efficiently inhibited in vitro by clodronate, an osteoactive, antiresorptive bisphosphonate. The IC50 of clodronate to inhibit MMP-1 is 150 microM. These findings suggest an extended and hitherto undescribed properties for clodronate/biphosphonates in prevention and treatment of tissue degradation in both bone and soft tissue destructive diseases.

Identification and characterization of gelatinases/type IV collagenases in jaw cysts.

The molecular mechanisms of jaw cyst expansion probably involve interactions of matrix metalloproteinases (MMPs) and the tissue inhibitors of MMPs (TIMPs). In this study, molecular species of gelatinases present in neutral salt extracts of cyst walls and cyst fluids were characterized by functional activity measurements (type I gelatin and alpha-casein zymography) and immunologically (Western-blotting). The effects of various protein thiol-group or cysteine-switch reactants involved in the activation of collagenases were studied on cyst gelatinases and a gelatinases purified from human gingival fibroblasts (72 kD MMP-2), gingival keratinocytes (92 kD MMP-9) and polymorphonuclear neutrophilic leukocytes (92 kD MMP-9). Western-blotting revealed the presence of both 92 kD (MMP-9) and 72 kD (MMP-2) gelatinases in cyst wall extracts and cyst fluids. Western-blot studies further suggested that jaw cyst gelatinases were only in part complexed with and thus inhibited by TIMP-1 or TIMP-2, suggesting that both MMP-9 and MMP-2 may participate in cyst expansion. MMP-2 was also partially fragmented to a 68 kD form and additional lower molecular weight proteinases (< 60 kD) were detected by alpha-casein zymography and by Western-blotting, suggesting proteolytic fragmentation. MMP-9 was at least partially activated by all protein-thiol group reactants and rather resistant to oxidative inhibition by hypochlorite (NaOCl); in contrast, MMP-2 was activated by APMA but not at all by gold thioglucose (GTG) and was clearly inactivated by hypochlorite (NaOCl).(ABSTRACT TRUNCATED AT 250 WORDS)

Free radicals and SOD activity of jaw cyst. Direct measurement and spin trapping studies by ESR.

Free radicals produced in the fluid of jaw cysts were directly measured at room temperature using ESR. With these samples, SOD activity of the cyst fluid was measured by the ESR spin trapping method with DMPO as a trapping agent. Freeze-dried samples of cyst fluid showed a broad ESR signal at g = 2.005. Relative signal intensity of samples from jaw cysts with inflammation was higher than jaw cysts without inflammation. SOD activity of cyst fluid with high viscosity showed higher values than that of cyst fluid with low viscosity. We suggest that free radicals produced in jaw cyst damage tissues while higher SOD activity of cyst fluid play a role in a self-defense mechanism against free radicals.

[Histoenzymological characteristics of epithelial cells in oral mucosal lesions and jaw cysts. Diagnostic significance]. / Caractères histoenzymologiques des cellules épithéliales dans les lésions de la muqueuse buccale et dans les kystes des maxillaires. Intérêt diagnostique.

An histoenzymological study (including oxidative enzymes, diaphorases, acid and alkaline phosphatases and naphtolesterases) of 41 biopsy and operation specimens revealed interesting factors in the diagnosis of some lesions of the buccal mucosa, and also of cysts and ameloblastomas of the jaw. When compared with normal buccal mucosa and epidermis, the enzymatic activities found in the oral lesions, fell into three different types. In non dysplasic leukoplakia, enzymatic activities were found that were similar to those of the epidermis (high oxidative activities, particularly prominent in basal cells and in the granular layer and esterasic activity beneath the keratinised layer). In lichen planus, some vacuolized or necrotic basal cells occurred which lacked enzymatic activity. In the upper layers, the distribution of the enzymes was irregular. In severe dysplasia and epidermoid carcinoma, numerous variations of oxidative, esterasic and acid phosphatase activities were seen from one cell to another. Among the lesions of the jaws, radicular cysts as well as dentigerous cysts, had low enzymatic activities, similar to those of normal buccal epithelium. The epidermoid cysts (keratocysts), because of their highly differentiated keratinization, like leukoplakia, had the same enzymatic activities as epidermis. The enzymatic activities of common ameloblastoma differed from those of malpighian tissues (low oxidative activities without decreasing gradient). Besides round epithelial nests, the stroma showed a high and widespread alkaline phosphatase activity, which indicated a low degree of odontogenic induction. Thus, this peculiar stromal activity may be useful in differentiating between cystic epidermoid varieties of ameloblastoma and the other epidermoid cysts of the jaws.

[Submicroscopic localization of endogenous peroxidase activity in the oral mucosal epithelium of man (author's transl)]. / Submikroskopische Lokalisation der endogenen Peroxidaseaktivität im Mundschleimhautepithel des Menschen.

Using electron microscopy, the authors localized endogenous peroxidase activity in the buccal mucosal and alveolar process epithelium. A positive reaction could be demonstrated in all epithelial layers. The number of positive structures was greatest in the spinous layer. The reaction product is of a granular nature and is localized in the microperoxysomes. The reaction of lipofuscin granules, lysosomes, and telolysosomes in the upper epithelial layers is considered to be of none enzymatic origin. The importance of endogenous peroxidase to tissue is discussed in detail.