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Biomedical subjects

D N Tatakis

Publications and source records attributed to D N Tatakis.

17 recordsLinked to original sources
PubMed1995

Periodontal regenerative potential of space-providing expanded polytetrafluoroethylene membranes and recombinant human bone morphogenetic proteins.

A concept of space provision to support skeletal repair has long been used in orthopedic and oral maxillofacial reconstructive therapy. More recently, this concept has been studied and adapted to periodontal reconstructive therapy. Other studies have demonstrated that skeletal tissues represent a significant reservoir of growth factors, including bone morphogenetic proteins. Such factors have been shown to stimulate skeletal repair in preclinical models and in clinical defects. We herein review studies using the critical size supraalveolar periodontal defect model in which clinically meaningful periodontal regeneration was achieved following reconstructive surgery, including space provision by reinforced expanded polytetrafluoroethylene membranes or including surgical implantation of recombinant human bone morphogenetic protein-2. Potential mechanisms involved in observed regeneration are discussed.

Bone Morphogenetic Proteins↗
PubMed1992

Human platelet factor 4 is a direct inhibitor of human osteoblast-like osteosarcoma cell growth.

The effect of purified human platelet factor 4, a platelet alpha-granule protein, on the growth of the human osteoblastic osteosarcoma cell lines Saos-2 and G-292 was investigated. Platelet factor 4 (20 ng/ml to 2 micrograms/ml) caused a significant, dose-dependent inhibition of human osteoblast-like osteosarcoma cell proliferation. Platelet factor 4 exerted its inhibitory effect under all growth conditions tested: serum-free, serum-stimulated and thrombin-stimulated. The platelet factor 4-induced cell inhibition was not associated with a cytotoxic effect on the cells (assessed by lactate dehydrogenase release). The inhibitory effect of platelet factor 4 was not affected by the presence of indomethacin in the cultures, indicating that the effect was prostaglandin-independent. These results suggest that platelet factor 4 has direct antitumor effects and that it may be important in pathological and physiological processes of bone.

Blood↗
PubMed1992

Effects of interleukin-1, tumor necrosis factor -beta, and forskolin on tissue plasminogen activator activity in human osteoblastic osteosarcoma cells.

The effects of interleukin-1 (IL-1), forskolin, and tumor necrosis factor beta (TNF-beta) on tissue plasminogen activator (t-PA) activity were studied in the human osteoblastic osteosarcoma cell line, G292. t-PA activity was measured in the cell media using the chromogenic substrate, S-2251. After a 24 hour incubation period, IL-1 increased t-PA in a dose-dependent manner. The effect of IL-1 at 10.0 U/ml was partially inhibited in the presence of indomethacin. Forskolin (1.0 microM) increased t-PA activity after 24 hours with the effects of combined treatment of IL-1 (1.0 U/ml, 10.0 U/ml) and forskolin being apparently additive in nature. TNF-beta (10(-8)-10(-7)M) also produced increased t-PA activity in the cell media after a 24 hour incubation period. These results suggest that the cytokines, IL-1 and TNF-beta, can increase t-PA activity in G292 cells and that there is both a cAMP-dependent as well as a cAMP-independent pathway involved in the regulation of this osteoblastic cell function.

Colforsin↗
PubMed1992

Second messenger systems stimulated by bradykinin in osteoblastic cells: evidence for B2 receptors.

The effects of bradykinin, analogs and inhibitors on the human osteoblastic osteosarcoma cell lines Saos-2 and G292 and on normal rat calvarial osteoblastic cells were investigated. In all cell types, bradykinin (1 nM-100 microM) caused significant time- and dose-dependent changes in the levels of inositol phosphates. Neomycin inhibited the inositol phosphate response to bradykinin, while indomethacin had no effect. Bradykinin also elicited a dose-dependent increase in free cytosolic calcium concentration. Bradykinin and T-kinin did not affect cyclic AMP levels in these cells. Doses of des-Arg9-bradykinin, a B1 receptor agonist, up to 100 nM did not stimulate the osteoblastic inositol phosphate response. In addition, the bradykinin-stimulated inositol phosphate response was unaffected by des-Arg9-[Leu8]-bradykinin, a B1 receptor antagonist, while it was inhibited by D-Arg-[Hyp3-[beta-(2-thienyl)-Ala]5,8-D-Phe7]-bradykinin, a B2 receptor antagonist. These results suggest that in osteoblastic cells the mechanism of action of bradykinin involves stimulation of the phosphoinositide metabolism and increases in cytosolic calcium levels through activation of B2 receptors.

Amino Acid Sequence↗
PubMed1991

Thrombin effects on osteoblastic cells. II. Structure-function relationships.

Thrombin has been shown to cause in vitro bone resorption and to stimulate osteoblastic cell proliferation, phosphoinositide turnover and cytosolic calcium levels. In the present study, the role of the active site of thrombin in its action on osteoblastic cells was investigated. Either hirudin or (4-amidinophenyl)methanesulfonyl fluoride inhibited, in a dose-dependent manner, the effects of thrombin on human osteoblast-like osteosarcoma cells (G292 and Saos-2 cell lines) and on normal rat calvarial osteoblastic cells. Thrombin-induced stimulation of cell proliferation, cytosolic calcium increases, and stimulation of phosphoinositide metabolism were concomitantly, and to a proportionally similar extent, inhibited. The inhibitors, when present in the absence of thrombin, did not affect the basal levels of cell functions. Both zeta-thrombin and gamma-thrombin, forms resulting from proteolytic cleavage of alpha-thrombin, were capable of stimulating the osteoblastic cells. These data indicate that thrombin's actions on osteoblast-like cells are dependent on the availability of its catalytic site.

Animals↗
PubMed1991

Effects of inositol trisphosphate on calcium mobilization in bone cells.

The effect of inositol 1,4,5 trisphosphate (IP3) on calcium mobilization was studied in human osteosarcoma lines, Saos-2 and G292, as well as isolated rat osteoblastic and osteoclastic cells. Cells were permeabilized with saponin and calcium mobilization was studied with the fluorescent dye, fura-2 in a recording spectrofluorometer. IP3 (10 microM) increased calcium release in all cell types studied. The effect was dependent on ATP and occurred in the presence of mitochondrial inhibitors. The effect was not seen with inositol 1-phosphate (IP) or inositol 1,4-diphosphate (IP2). Inositol 1,3,4,5 tetrakisphosphate (IP4) appeared to elicit a decrease in the calcium released. Depletion of the intracellular pool with the calcium ionophore, ionomycin, as well as incubation with the inhibitor of intracellular calcium mobilization, TMB-8, obliterated the IP3 effect. The results are consistent with the hypothesis that increases in IP3 can cause a rapid elevation of bone cell cytosolic calcium.

Animals↗
PubMed1991

Prostaglandin-induced changes in calcium uptake and cAMP production in osteoblast-like cells: role of protein kinase C.

Phorbol esters were used to evaluate the putative effect of protein kinase C (PKC) activation on prostaglandin E2 (PGE2)-induced increases in calcium uptake and cAMP production in the human osteoblastic osteosarcoma cell line, Saos-2. The cells were pretreated for 15 min with phorbol myristate acetate (PMA) followed by a 5 min incubation with PGE2. Calcium uptake was measured with 45Ca and cAMP by radioimmunoassay. A significant increase in calcium uptake was noted in the PGE-treated cells compared with controls and preincubation with the PMA caused a significant decrease in this response. Preincubation with PMA also inhibited the PGE2-induced increase in cAMP under identical conditions. The effect of PMA on the cAMP response was not influenced by the addition of a phosphodiesterase inhibitor. PMA had no effect on the basal levels of either calcium uptake or cAMP production. Likewise, the inactive phorbol esters, phorbol 12,13-didecanoate (PDD) and 4 alpha-phorbol 12-myristate, 13-acetate (4 alpha), had no effect on either basal levels of these parameters or on the PGE2-induced increases. These results suggest that PKC is involved in the down-regulation of PGE2-induced increases in calcium uptake and cAMP production in the Saos-2 osteoblastic cell line.

Calcium↗
PubMed1991

Gingival crevicular fluid elastase-inhibitor complex: correlation with clinical indices and subgingival flora.

This investigation analyzed, in a cross-sectional study, the possible relationship between gingival crevicular fluid (GCF) elastase-like protease (ELP) levels and the periodontal clinical parameters or the presence of specific bacteria in subgingival plaque. A total of 388 periodontal sites from 8 adult periodontitis patients were examined for plaque index (PII), gingival index (GI), pocket depth (PD) and alveolar bone loss (ABL). GCF ELP levels were determined as ELP alpha-1 protease inhibitor (ELP-alpha 1-PI) complex levels with a commercially available ELISA. Subgingival plaque samples were tested for the presence of Bacteroides gingivalis, B. intermedius and Actinobacillus actinomycetemcomitans by indirect immunofluorescence (IF) microscopy. GCF ELP-alpha 1-PI levels were then correlated with clinical periodontal indices and proportions of IF-positive bacteria per site. Statistically significant positive correlations were found between GCF ELP-alpha 1-PI concentrations and subgingival Bacteroides proportions. When the sites examined were analyzed depending on the level of each clinical parameter, the levels of these correlations changed. A. actinomycetemcomitans correlated highly (r = 0.716) with ABL for sites with low GI score. The correlations between GCF ELP-alpha 1-PI and B. gingivalis (r = 0.642) or B. intermedius (r = 0.774) were the highest for ABL less than or equal to 20% and PD less than or equal to 3 mm, respectively. The strong association between GCF ELP-alpha 1-PI concentrations and subgingival bacteria previously associated with advancing periodontitis indicates that measurement of GCF ELP-alpha 1-PI concentrations may be useful in the evaluation of periodontal sites, especially those with very little or no tissue destruction.

Actinobacillus↗
PubMed1991

Recombinant interleukin-1 (IL-1) stimulates prostaglandin E2 production by osteoblastic cells: role of calcium, calmodulin, and cAMP.

Interleukin-1 (IL-1) has been previously shown to stimulate prostaglandin E2 (PGE2) production by osteoblastic cells. This IL-1 effect has also been shown to be potentiated by parathyroid hormone (PTH), which activates both the calcium and the cAMP signal transduction pathways in osteoblastic cells. In the present study, the role of calcium, calmodulin, and cAMP in potentiating the IL-1 effect was examined. The calcium channel blocker verapamil (100 microM) completely inhibited the IL-1 effect. Similarly, the calmodulin antagonist W-7 (50 microM) inhibited the IL-1-induced stimulation. Conversely, the calcium ionophore A23187 (0.1 microM) potentiated the IL-1 effect. The phosphodiesterase inhibitor isobutyl-methylxanthine (IBMX; 100 microM), which elevates cAMP levels in the cells, had a strong potentiating effect on the IL-1-induced PGE2 production. These results suggest that both the calcium and the cAMP second messenger systems can modulate the IL-1 effect on osteoblastic cells.

1-Methyl-3-isobutylxanthine↗
PubMed1990

Effects of tumor necrosis factor alpha on parathyroid hormone-induced increases in osteoblastic cell cyclic AMP.

Tumor necrosis factor alpha (10(-10) - 10(-8) M) had no effects on cyclic AMP production by the osteoblastic osteosarcomal cells, Saos-2 and G292, or normal rat calvarial cells. The cytokine did, however, inhibit the parathyroid hormone (PTH)-induced effect on cyclic AMP in the Saos-2 and normal rat osteoblastic cells. This inhibitory effect did not occur on prostaglandin E2-induced cyclic AMP increases in the osteoblastic cells. Interleukin-1 (10 U/ml-100 U/ml) did not produce any effect on basal levels or PTH-induced cyclic AMP increases in these cells.

Animals↗
PubMed1990

Chronic ulcerative stomatitis associated with a specific immunologic marker.

Four elderly women with chronic oral ulcerations are described. The lesions are chronic, erosive, or ulcerative; occur on the gingival, buccal, or lingual mucosa; and may occur in the form of desquamative gingivitis. The histopathologic findings are nondiagnostic. The disease is refractory to local and systemic corticosteroids, but treatment with hydroxychloroquine may be effective. Both in vivo binding to the oral mucosa and skin of a stratified epithelium-specific antinuclear antibody and high titers of these antibodies in serum are markers of this disease, which we refer to as chronic ulcerative stomatitis associated with stratified epithelium-specific antinuclear antibody.

Aged↗
PubMed1989

Thrombin's effects on osteoblastic cells. I. Cytosolic calcium and phosphoinositides.

Thrombin, a blood coagulation factor, has been shown to be a very effective in vitro bone resorbing agent whose mechanism of action on osteoblastic cells remains to be elucidated. In the present study, the effects of highly purified human thrombin on Saos-2 and G292 cells, two human osteoblast-like osteosarcoma cell lines, were investigated. Thrombin (0.6-16 U/ml) caused a significant, dose-dependent increase in osteoblastic cell proliferation. Thrombin also elicited a dose-dependent increase in cytosolic calcium concentration in both Saos-2 and G292 cells (maximal increases were 38% and 200% over baseline, respectively). Addition of thrombin to the osteoblast-like cells resulted in significant time- and dose-dependent changes in phosphoinositide levels: the percentage of inositol monophosphate levels were decreased, whereas the percentage of inositol bisphosphate, inositol trisphosphate and inositol tetrakisphosphate levels were increased. The relative magnitude of the changes in phosphoinositide levels was similar to the changes in cytosolic calcium concentration. These results suggest that thrombin's mechanism of action on bone cells may involve increases in cytosolic calcium levels and in phosphoinositide metabolism.

Bone Resorption↗
PubMed1989

Recombinant human lymphotoxin effects on osteoblastic cells.

Lymphotoxin, or tumor necrosis factor beta, has been shown to be a potent bone resorbing cytokine. In the present study, the effect of recombinant human lymphotoxin on osteoblastic cell proliferation and prostaglandin synthesis was investigated. Lymphotoxin (10(-10)-10(-7) M) caused a significant, dose-dependent decrease of rat osteoblastic cell proliferation. This appeared to be an indirect, prostaglandin-dependent action, since in the presence of indomethacin (1 microM) the lymphotoxin effect was reversed. Subsequently, prostaglandin E2 and prostacyclin (assayed as 6-keto-prostaglandin F1 alpha) levels produced by the osteoblastic cells in response to lymphotoxin were measured. The cytokine caused a dose-dependent increase of these arachidonic acid metabolites, with the maximum effect at 10(-8) M. These results suggest that lymphotoxin's mechanism of action on bone may involve increases in arachidonic acid metabolite synthesis and an indirect, prostanoid-mediated decrease in the proliferation rate of osteoblastic cells.

Animals↗
PubMed1989

Leukotrienes in orthodontic tooth movement.

Prostaglandins (PGs) and leukotrienes (LTs) are products of arachidonic acid conversion. PGs have an established role in mediating orthodontic tooth movement. The role of LTs in modulating or mediating orthodontic tooth movement was investigated in this study. One hundred thirty-two Sprague-Dawley rats were used; the animals weighed 300 to 400 gm with equal numbers of male and female rats. They were divided into five main groups of 24 animals each and a sham group of 12 animals. An orthodontic appliance was placed and activated on all the animals except the sham group; in this group the appliances were not active. Each main group was given one of the following treatments daily: distilled water, 5% gum arabic solution, PG synthesis inhibitor indomethacin, LT synthesis inhibitor AA861, and a combination of both drugs. Each group was divided into six subgroups of four animals; the animals were killed at either 1, 3, 5, 7, 10, or 14 days, and tooth movement measured. The three sham subgroups received distilled water and were killed at 1, 7, or 10 days. The first maxillary molar (the moved tooth) and surrounding tissues were removed from all animals in the sham group and the subgroups killed at 1, 7, and 10 days in the gum arabic solution group and the LT synthesis inhibitor group. Prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) were extracted, measured with radioimmunoassay (RIA), and standardized per milligram of protein in the sample. A significant inhibition of tooth movement occurred beginning on day 7 in the indomethacin, AA861, and combination groups; there was no significant difference among these groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Recombinant interleukin-1 stimulates prostaglandin E2 production by osteoblastic cells: synergy with parathyroid hormone.

Recombinant mouse IL-1 (Interleukin-1) has been shown to be capable of stimulating prostaglandin E2 (PGE2) production by isolated rat osteoblastic cells in a dose-dependent manner. The rapidity of the effect (1 hour) and the potency of IL-1 (5 x 10(-12) M) in producing this effect suggest that IL-1 may exert some of its effects on bone via PGE2. Parathyroid hormone (PTH) appears to have a strong synergistic effect with IL-1. These data further substantiate the role of IL-1 in bone physiology.

Animals↗
PubMed1986

The use of monoclonal antibodies to detect Bacteroides gingivalis in biological samples.

Hybridomas were established which produce monoclonal antibodies specific for Bacteroides gingivalis, a pathogen associated with human periodontal disease. Spleen cells from BALB/c mice immunized with formalinized B. gingivalis were fused with Sp2/0-Ag14 myeloma cells. Of 1,050 wells with positive growth, 60 contained antibody reactive with the immunizing strain of B. gingivalis by enzyme-linked immunosorbent assay. Expansion of these cultures and cloning by limited dilution resulted in 28 clones which reacted with B. gingivalis but not with other orals and nonoral black-pigmented Bacteroides species or any of 29 representative strains of other oral bacteria. Of these 28 clones, 14 were also specific for B. gingivalis by indirect immunofluorescence microscopy. One clone, BBG-12 producing immunoglobulin G2b(kappa), was chosen to identify B. gingivalis in subgingival plaque because of its high reactivity in indirect immunofluorescence assays. This antibody reacted strongly with all 17 representative B. gingivalis strains obtained from diverse sources. Furthermore, when this reagent was applied to subgingival plaque samples, B. gingivalis was stained with high specificity and low background fluorescence, indicating that it may be useful for clinical identification of this organism.

Antibodies, Bacterial↗