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PubMed2004

Enhanced cementum formation in experimentally induced cementum defects of the root surface with the application of recombinant basic fibroblast growth factor in collagen gel in vivo.

BACKGROUND: Therapies using biologically active, soluble factors such as growth factors or cytokines have been investigated for potential clinical use in regenerating lost periodontal tissue due to periodontitis. Basic fibroblast growth factor (bFGF, FGF-2) is a multifunctional growth factor that has a variety of effects including induction of proliferation and morphogenesis in a wide range of cells and tissues including periodontal ligament tissue. METHODS: In this study, we examined the effects of bFGF on the regeneration of cementum and periodontal ligament in experimentally induced partial defects in a beagle dog model. bFGF in a collagen gel was applied to the defects and root surfaces, and the teeth were replanted. RESULTS: Eight weeks post-surgery, formation of cementum on denuded dentin was enhanced by application of 0.1, 1, or 5 microg of bFGF in a collagen gel compared to collagen gel containing vehicle. Histological analyses revealed that at 4 weeks post-surgery, random periodontal ligament fibers had bound to dentin, but were attached only to denuded dentin to which 0.1, 1, or 5 microg of bFGF in collagen gel had been applied. At 8 weeks post-surgery, we observed the formation of dense fibers bound to alveolar bone and newly synthesized cementum in teeth treated with 1 microg of bFGF. CONCLUSION: These results suggest that basic fibroblast growth factor in a collagen gel is a suitable therapy for damaged periodontal ligament and could lead to readily achievable methods of treatment for periodontal disease.

Alveolar Process↗
PubMed1997

Upmodulation of multinucleated cell formation in long-term human bone marrow cultures by leukaemia inhibitory factor (LIF).

Inflammatory processes are mediated by many cellular events involving different cell types (leukocytes, monocytes, stromal cells, etc.). Numerous soluble mediators regulate these reactions, including leukaemia inhibitory factor (LIF), a cytokine which may play an important role in inducing acute-phase protein synthesis by hepatocytes during inflammation. This study was designed to determine the effects of LIF on the human monocyte/macrophage lineage and provide a better definition of its behaviour during systemic inflammation. In-vitro exposure of human long-term bone marrow cultures to recombinant human LIF significantly increased (about two-fold) the number of multinucleated cells (MNC) formed after three weeks of culture. These LIF-induced MNC expressed tartrate-resistant acid phosphatase, and LIF increased this intracellular activity by about 50%. MNC displayed phagocytotic activity but were unable to degrade sperm whale dentin or respond to human calcitonin. They did not possess the main characteristics of osteoclasts and were in fact macrophage polykaryons. Our results demonstrate for the first time that LIF can induce macrophage polykaryon formation from human bone marrow culture, suggesting that this factor not only produces leukocytes but also has a direct influence on the monocyte/macrophage lineage.

Acid Phosphatase↗
PubMed1981

Purification, composition, and 31P NMR spectroscopic properties of a noncollagenous phosphoprotein isolated from chicken bone matrix.

Fractionation of the EDTA-soluble, noncollagenous proteins of the organic matrix of chicken bone by Sephadex G-100 molecular sieving has revealed that the majority of the organic phosphorus is present in two fractions, from one of which a homogeneous phosphoprotein has been isolated. The purified phosphoprotein has an apparent molecular weight of 12,000 and contains both O-phosphoserine and O-phosphothreonine. 31P-NMR spectroscopy demonstrates that all of the organic phosphorus exists in the form of phosphomonoesters which have an average pK2 of 6.8. The phosphoprotein is highly acidic due to its high content of dicarboxylic acids in addition to the presence of organic phosphorus. The characteristic amino acid composition of the phosphoprotein establishes its noncollagenous nature and highlights the differences among bone, dentin, and enamel phosphoproteins. The absence of gamma-carboxyglutamic acid distinguishes it from osteocalcin, the noncollagenous gamma-carboxyglutamic acid-containing peptide of bone matrix.

Amino Acids↗
PubMedDate not supplied

Investigation of the role of human breast milk in caries development.

PURPOSE: The objective of this study was to determine the caries-related risk associated with human breast milk (HBM). METHODS: First, the plaque pH of 18 children (12-24 months) was monitored before and after a five-minute feeding with HBM to determine the pH drop and minimum pH obtained. Second, Streptococcus sobrinus 6715 was cultured for 3 hr in HBM, and the increase in the number of colony forming units (cfus) and the culture pH was measured. Third, HBM was incubated for 24 hr with powdered enamel to determine the solubility of mineral in the absence of bacteria. Fourth, HBM was mixed with acid to determine the buffering capabilities. Finally, enamel windows were created on extracted premolar crowns (N = 33) that were colonized with Mutans Streptococci and incubated with HBM. Caries was assessed visually and radiographically for 12 weeks. RESULTS: One- and two-way ANOVAs of these five assays demonstrated that HBM did not cause a significant drop in plaque pH when compared to rinsing with water; HBM supported moderate bacterial growth; calcium and phosphate were actually deposited onto enamel powder after incubation with HBM; the buffer capacity of HBM was very poor; and HBM alone did not cause enamel decalcification even after 12 weeks exposure. However, when supplemented with 10% sucrose, HBM caused dentinal caries in 3.2 weeks. CONCLUSION: It is concluded that human breast milk is not cariogenic.

Analysis of Variance↗
PubMed1996

Disturbed enamel mineralization in a rat incisor model.

Possession of full-thickness hard enamel appears to be one of the indispensable life-saving characteristics of rats. Previous studies by Suga and his colleagues and by others demonstrated that various types of malformation are evoked in continuously erupting rat incisors. In the current report, we directed our effort to oversee various types of enamel malformation caused experimentally in rat incisors. We surveyed the specimens collected by Suga and his colleagues, as well as specimens we obtained. From the results, it is conceivable that perturbation of the programmed sequential events during enamel development is a major factor in the establishment of enamel malformation. Animal studies with either 1-hydroxyethylidene-1,1-bisphosphonate (HEBP) or a multidentate phosphonic acid (EDTPO) confirmed that dentin mineralization provides a certain inductive effect on the secretion of enamel matrix and subsequent enamel crystallization. Our recent studies using anti-microtubular agents led to the conclusion that the acceleration of mineralization in outer enamel is a type of enamel malformation, most likely due to disruption of the cellular regulation of calcium transport under severe toxic regimens. In future work, experimental approaches combining measurements of kinetic factors with static observation of enamel lesions are required before we can gain a comprehensive understanding of the pathogenesis of disturbed enamel mineralization. The kinetic factors to be considered include the rates of tissue apposition and tooth eruption which determine the total volume of tooth substance formed, and the rate of mineral accretion. Furthermore, information as to the composition, crystallinity, solubility, and mechanical properties of enamel defects is needed before we can assess the susceptibility of teeth having those lesions to caries and other physico-chemical attacks in the oral environment.

Ameloblasts↗
PubMed2006

New 19-nor-(20S)-1alpha,25-dihydroxyvitamin D3 analogs strongly stimulate osteoclast formation both in vivo and in vitro.

2-Methylene-19-nor-(20S)-1alpha,25-dihydroxyvitamin D3 (2MD), an analog of 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3], has been shown to strongly induce bone formation both in vitro and in vivo. We have synthesized four substituents at carbon 2 of 2MD (2MD analogs), four stereoisomers at carbon 20 of the respective 2MD analogs (2MD analog-C20 isomers) and four 2MD analogs with an oxygen atom at carbon 22 (2MD-22-oxa analogs) and examined their ability to stimulate osteoclastogenesis and induce hypercalcemia. 2MD analogs were 100 times as potent as 1alpha,25(OH)2D3 in stimulating the formation of osteoclasts in vitro and in inducing the expression of receptor activator of NF-kappaB ligand (RANKL) and 25-hydroxyvitamin D3-24 hydroxylase mRNAs in osteoblasts. The osteoclast-inducing activities of 2MD analog-C20 isomers and 2MD 22-oxa analogs were much weaker than those of 2MD analogs. In addition, the activity of a 2MD analog in inducing dentine resorption was much stronger than that of 1alpha,25(OH)2D3 in the pit formation assay. Affinities to the vitamin D receptor and transcriptional activities of these compounds did not always correlate with their osteoclastogenic activities. Osteoprotegerin-deficient (OPG-/-) mice provide a suitable model for investigating in vivo effects of 2MD analogs because they exhibit extremely high concentrations of serum RANKL. The same amounts of 2MD analogs and 1alpha,25(OH)2D3 were administered daily to OPG-/- mice for 2 days. The elevation in serum concentrations of RANKL and calcium was much greater in 2MD analog-treated OPG-/- mice than in 1alpha,25(OH)2D3-treated ones. A 2MD analog was much more potent than 1alpha,25(OH)2D3 in causing hypercalcemia and in increasing soluble RANKL with enhanced osteoclastogenesis even in wild-type mice. In contrast, the administration of the 2MD analog to c-fos-deficient mice failed to induce osteoclastogenesis and hypercalcemia. These results suggest that new substituents at carbon 2 of 2MD strongly stimulate osteoclast formation in vitro and in vivo, and that osteoclastic bone resorption is indispensable for their hypercalcemic action of 2MD analogs in vivo.

Animals↗
PubMed1992

Effects of non-collagenous proteins on the formation of apatite in calcium beta-glycerophosphate solutions.

The effects of the non-collagenous proteins; osteonectin, bone Gla protein and dentine phosphoprotein, on the formation of apatite were studied in calcium beta-glycerophosphate solutions containing catalytic amounts of alkaline phosphatase under physiological conditions. In the system used, calcium phosphate precipitates de novo at levels of supersaturation precisely determined through the enzymatic hydrolysis of beta-glycerophosphate. At 1.7 mM of calcium beta-glycerophosphate, calcium phosphate precipitated when inorganic phosphate accumulated to about 1.4 mM. In the presence of the proteins, however, a greater accumulation of inorganic phosphate was needed for calcium phosphate to precipitate, suggesting that a higher degree of supersaturation, though still a slight undersaturation with respect to dicalcium phosphate dihydrate, is required for calcium phosphate to precipitate in the presence of the proteins. At the same protein (micrograms/ml) concentration, dentine phosphoprotein was approximately four times as effective as bone Gla protein, which was about twice as effective as osteonectin in delaying precipitation. The proteins also retarded subsequent crystal growth, with apatite formed in the presence of the more inhibitory proteins having the smallest crystals, especially in width.

Alkaline Phosphatase↗
PubMedDate not supplied

A sequential culture approach to study osteoclast differentiation from nonadherent porcine bone marrow cells.

A "sequential culture step" system was devised to study osteoclast differentiation from newborn porcine bone marrow cells. Nonadherent cells were collected from cultures of bone marrow cells, and subsequently precultured at a low cell density in low-serum medium supplemented with L929-conditioned medium (L9-CM) derived M-CSF/CSF-1. After 4 d, adherent cells mainly composed of M-CSF-dependent macrophage/osteoclast progenitors, but devoid of stromal-like cells, were further cultured in medium supplemented with L9-CM and CM derived from serum-free cultures of fetal rat calvarial bones. This phase was characterized by a rapid induction of mono- and multinucleated (pre)osteoclast-like cells, positive for cytochemical TRAP activity, but negative for nonspecific esterase (NSE) staining. The presence of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] stimulated osteoclast generation, whereas calcitonin treatment significantly inhibited this process. The osteoclastic nature of the cells was confirmed by the occurrence of extensive, characteristic bone resorption on dentin slices, which was associated with release of type I collagen N-telopeptides from the bone matrix into the culture medium. The presence of a DNA synthesis inhibitor (HU) during the first 3 d of culture completely inhibited osteoclast formation, whereas HU treatment during the last phase did not affect production of multinucleated osteoclast-like cells. Likewise, a specific antibody directed against M-CSF during the first preculture period, completely abolished osteoclast formation. Adding the antibody during the last phase of the culture, however, strongly inhibited multinucleated osteoclast formation, accompanied by a significant increase in a mononuclear TRAP-positive, NSE-positive (osteoclast precursor) cell fraction. These results indicate that M-CSF is essential for progenitor proliferation as well as for (pre)osteoclast maturation and/ or fusion into multinucleated cells, but also suggest that additional soluble (bone-derived) factors are involved as cofactors in the differentiation process to committed mononuclear osteoclast precursors. The porcine marrow culture approach provides a suitable model system to investigate specific soluble osteoclast-inducing factors affecting different stages of osteoclast development.

Animals↗
PubMed1995

Induction of bone resorbing-activity by mouse stromal cell line, MC3T3-G2/PA6.

Unfractionated mouse long-bone cells prestimulated with rat parathyroid hormone (PTH) for 7 days (PTH-prestimulated long-bone cells; PTH-psLB cells) contained about 20% tartrate-resistant acid phosphatase (TRAP)-positive mononuclear cells and about 0.2% TRAP-positive multinucleate cells. When PTH-psLB cells (1.0 x 10(5)/slice) were cultured on dentine slices, about 100 resorption lacunae (pits) per slice were formed by 6 h after the start of culture, while the number of TRAP-positive multinucleate cells on the dentine slices did not increase. When the number of inoculated cells was plotted versus the number of pits formed during the 6-h cultivation, a sigmoid curve was generated. When PTH-psLB cells (1.0 x 10(3)/slice) were cocultured with various mouse stromal cell lines, the MC3T3-G2/PA6 line was found to increase the number of pits. Since this activity was manifested within a short period of time (4 h), and as there was no change in the number of TRAP-positive multinucleate cells, we postulate that the activity of MC3T3-G2/PA6 is exerted on mature osteoclastic cells capable of resorbing bone rather than on some differentiation step of the osteoclast cell lineage. With respect to the mechanism of expression of this activity, it is unlikely that MC3T3-G2/PA6 produces a soluble factor, because no activity was seen when MC3T3-G2/PA6 and PTH-psLB cells were cultured separately across a membrane in a Transwell. These results suggest that cell-to-cell contact and communication between PTH-psLB cells and MC3T3-G2/PA6 may be a crucial event for the stimulation of osteoclastic bone resorption by MC3T3-G2/PA6.

Animals↗
PubMed2001

Cellular mechanisms of bone resorption in breast carcinoma.

The cellular mechanisms that account for the increase in osteoclast numbers and bone resorption in skeletal breast cancer metastasis are unclear. Osteoclasts are marrow-derived cells which form by fusion of mononuclear phagocyte precursors that circulate in the monocyte fraction. In this study we have determined whether circulating osteoclast precursors are increased in number or have an increased sensitivity to humoral factors for osteoclastogenesis in breast cancer patients with skeletal metastases (+/- hypercalcaemia) compared to patients with primary breast cancer and age-matched normal controls. Monocytes were isolated and cocultured with UMR 106 osteoblastic cells in the presence of 1,25 dihydroxyvitamin D3[1,25(OH)2D3] and human macrophage colony stimulating factor (M-CSF) on coverslips and dentine slices. Limiting dilution experiments showed that there was no increase in the number of circulating osteoclast precursors in breast cancer patients with skeletal metastases (+/- hypercalcaemia) compared to controls. Osteoclast precursors in these patients also did not exhibit increased sensitivity to 1,25(OH)2D3or M-CSF in terms of osteoclast formation. The addition of parathyroid hormone-related protein and interleukin-6 did not increase osteoclast formation. The addition of the supernatant of cultured breast cancer cell lines (MCF-7 and MDA-MB-435), however, significantly increased monocyte-osteoclast formation in a dose-dependent fashion. These results indicate that the increase in osteoclast formation in breast cancer is not due to an increase in the number/nature of circulating osteoclast precursors. They also suggest that tumour cells promote osteoclast formation in the bone microenvironment by secreting soluble osteoclastogenic factor(s).

Aged↗
PubMed1993

Soluble interleukin-6 receptor triggers osteoclast formation by interleukin 6.

It has been reported that soluble interleukin (IL)-6 receptor (sIL-6R) is detected in the serum of healthy individuals and its level is increased in patients with multiple myeloma and human immunodeficiency virus infection. Although several reports have suggested that sIL-6R potentiates IL-6 action, its physiological role remains unclear. In this study, we examined the role of sIL-6R on osteoclast formation by IL-6, using a coculture of mouse osteoblasts and bone marrow cells. Neither recombinant mouse IL-6 (mIL-6) nor mouse sIL-6R (smIL-6R) induced osteoclast-like multinucleated cell (MNC) formation when they were added separately. In contrast, simultaneous treatment with mIL-6 and smIL-6R strikingly induced MNC formation. These MNCs satisfied major criteria of authentic osteoclasts, such as tartrate-resistant acid phosphatase (TRAP) activity, calcitonin receptors, and pit formation on dentine slices. The MNC formation induced by mIL-6 and smIL-6R was dose-dependently inhibited by adding monoclonal anti-mouse IL-6R antibody (MR16-1). It is likely that osteoblasts and osteoclast progenitors are capable of transducing a signal from a complex of IL-6 and sIL-6R through gp130, even though they may have no or a very small number of IL-6Rs. Factors such as IL-11, oncostatin M, and leukemia inhibitory factor, which are known to exert their functions through gp130 (the signal-transducing chain of IL-6R), also induced MNC formation in our coculture system. These results suggest that increased circulating or locally produced sIL-6R induces osteoclast formation in the presence of IL-6 mediated by a mechanism involving gp130. This may play an important physiological or pathological role in conditions associated with increased osteoclastic bone resorption.

Animals↗
PubMed1994

Influence of marginal opening on microleakage of cemented artificial crowns.

This study investigated the relationship between marginal opening and microleakage. Standardized preparations were made on intact human premolars, and copings were cast in a base metal alloy by use of conventional techniques. The castings were randomly assigned to the following luting agent groups: zinc phosphate cement, polycarboxylate cement, glass ionomer cement, phosphate ester composite resin, and a composite resin with a NPG-GMA dentinal bonding agent and were cemented in a standardized manner. The marginal openings between teeth and castings were measured, and microleakage was determined at the same points. Within the confines of the in vitro model used, no significant correlation between marginal opening and microleakage was established for either pooled data or individual luting agent groups.

Analysis of Variance↗
PubMed1976

Dental phosphoprotein-induced formation of hydroxylapatite during in vitro synthesis of amorphous calcium phosphate.

(Ethylenedinitrilo)tetraacetic acid soluble phosphoproteins were isolated from rat incisor and bovine unerupted teeth. This material was examined for its effect on the stability of amorphous calcium phosphate in vitro. When the precipitation of amorphous calcium phosphate was attempted in the presence of small amounts of these phospho-proteins, an apatite-like mineral was observed to form, which was approximately 60% crystalline, as determined by infrared measurements. This apatite phase could not be induced by addition of phosphoprotein after the precipitation reaction. The organic phosphate bound to these phosphoproteins was shown to be directly responsible for the formation of the apatite phase, since removal of 60% of the covalently bound phosphate with alkaline phosphatase destroyed the protein's ability to induce hydroxylapatite formation. The properties of the dental phosphoproteins appear to be consistent with their possible involvement in the development of the mineral phase of dentine.

Amino Acids↗
PubMed1995

C-type natriuretic peptide increases bone resorption in 1,25-dihydroxyvitamin D3-stimulated mouse bone marrow cultures.

Most agents that regulate osteoclast bone resorption exert their effects indirectly, through the osteoblast. Nitric oxide, which stimulates soluble guanylyl cyclase, has been reported to inhibit osteoclast bone resorption directly, by a cGMP-independent mechanism (1). In this report, we demonstrate that C-type natriuretic peptide (CNP), an activator of membrane-bound guanylyl cyclase, stimulates bone resorption by osteoclast-containing 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3)-stimulated mouse bone marrow cultures. Quantitative reverse transcription polymerase chain reaction assays and anti-CNP immunocytochemistry were used to demonstrate that CNP is expressed in mouse marrow cells cultured in the presence, but not the absence, of, 1,25-(OH)2D3. mRNA for guanylyl cyclase type B, the receptor for CNP, was expressed in cultures independent of 1,25-(OH)2D3. CNP (1 and 10 microM) elevated cGMP production in marrow cultures to 350 and 870%, respectively, of control values. 10 microM CNP increased osteoclast bone resorptive activity, measured by the resorption area on whale dentine wafers, or by the NH4Cl-inhibitable release of [3H]proline from radiolabeled bone chips, to 214 and 557% of control, respectively, without affecting osteoclast formation. Bone resorption by the marrow cultures was inhibited by 7F9.1, a monoclonal antibody raised against CNP, but not by control antibodies. These results indicate that CNP is a potent activator of osteoclast activity and may be a novel local regulator of bone remodeling.

Animals↗
PubMed1993

The effect of prenatal caffeine exposure on the enamel surface of the first molars of newborn rats.

Timed-pregnant rats were randomly divided into three groups at day 7 of gestation. A caffeine tablet was implanted subcutaneously in the experimental group and a placebo tablet in the control group. The third group was used as surrogate dams. At birth, eight randomly selected pups born either to the experimental or control dams were placed with surrogate dams that had produced pups on the same day; these were then used in either the experimental or the control group, and so the surrogate dams raised pups that came from either the experimental or control group. At day 22 after birth, the pups were killed, and their first and second maxillary and mandibular molars were removed. They were then placed in a specially designed chamber and exposed to an acid solution. The outflowing acid solution was collected every 20 min and up to 80 min. Then the calcium, phosphorus, and magnesium contents of each fraction were measured. The enamel surfaces of untreated and acid-treated first molars of the caffeine and control groups were examined by scanning electron microscopy. Untreated teeth were powdered and separated into enamel and dentine. Pure enamel samples were examined with a Gandolfi X-ray powder camera to measure the crystallite size. At 20-, 40- and 60-min intervals, calcium and phosphorus contents of the first molars of the caffeine group were significantly higher than those of the control. The enamel surface of the untreated and acid-treated first molars of the caffeine group had significantly different scanning microscopic appearances from those of the non-caffeine untreated and acid-treated control groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2003

Effect of soluble receptors to interleukin-1 and tumor necrosis factor alpha on experimentally induced root resorption in rats.

OBJECTIVE: In this study, the role of the inflammatory cytokines interleukin-1 (IL-1) and tumor necrosis factor alpha (TNFalpha) in the course of mechanically induced root resorption was investigated. METHODS: Mechanical induction of root resorption was performed on the upper left first molars in 18 male Wistar rats according to the method of Nakane and Kameyama. Starting on day minus 1, six animals received daily intraperitoneal injections of 2 ml of 1 micro g/ml soluble receptors to IL-1 (sIL-1RII) and another six animals were administered the same dose of soluble receptors to TNFalpha (sTNFalpha-RI). Six animals served as a control. On d 7 the left maxillae were prepared for histological and morphometric analysis of the extent of the root resorption that had developed. RESULTS: The qualitative and quantitative results demonstrated that in both receptor groups the amount of root resorption was significantly reduced. Especially following systemic application of sTNFalpha-RI, root resorption was nearly completely prevented. CONCLUSIONS: Our results indicate that IL-1 and more particularly TNFalpha are important for the induction and the further process of mechanically induced root resorption in the rat.

Acid Phosphatase↗
PubMed1999

Protective immunity against Streptococcus mutans infection in mice after intranasal immunization with the glucan-binding region of S. mutans glucosyltransferase.

Here we present the construction and characterization of a chimeric vaccine protein combining the glucan-binding domain (GLU) of the gtfB-encoded water-insoluble glucan-synthesizing glucosyltransferase enzyme (GTF-I) from Streptococcus mutans and thioredoxin from Escherichia coli, which increases the solubility of coexpressed recombinant proteins and stimulates proliferation of murine T cells. The protective potential of intranasal (i.n.) immunization with this chimeric immunogen was compared to that of the GLU polypeptide alone in a mouse infection model. Both immunogens were able to induce statistically significant mucosal (salivary and vaginal) and serum responses (P < 0.01) which were sustained to the end of the study (experimental day 100). Following infection with S. mutans, sham-immunized mice maintained high levels of this cariogenic organism ( approximately 60% of the total oral streptococci) for at least 5 weeks. In contrast, animals immunized with the thioredoxin-GLU chimeric protein (Thio-GLU) showed significant reduction (>85%) in S. mutans colonization after 3 weeks (P < 0.05). The animals immunized with GLU alone required 5 weeks to demonstrate significant reduction (>50%) of S. mutans infection (P < 0.05). Evaluation of dental caries activity at the end of the study showed that mice immunized with either Thio-GLU or GLU had significantly fewer carious lesions in the buccal enamel or dentinal surfaces than the sham-immunized animals (P < 0.01). The protective effects against S. mutans colonization and caries activity following i.n. immunization with GLU or Thio-GLU are attributed to the induced salivary immunoglobulin A (IgA) anti-GLU responses. Although in general Thio-GLU was not significantly better than GLU alone in stimulating salivary IgA responses and in protection against dental caries, the finding that the GLU polypeptide alone, in the absence of any immunoenhancing agents, is protective against disease offers a promising and safe strategy for the development of a vaccine against caries.

Administration, Intranasal↗
PubMed1995

Teeth and tooth nerves.

(1) Although our knowledge on teeth and tooth nerves has increased substantially during the past 25 years, several important issues remain to be fully elucidated. As a result of the work now going on at many laboratories over the world, we can expect exciting new findings and major break-throughs in these and other areas in a near future. (2) Dentin-like and enamel-like hard tissues evolved as components of the exoskeletal bony armor of early vertebrates, 500 million years ago, long before the first appearance of teeth. It is possible that teeth developed from tubercles (odontodes) in the bony armor. The presence of a canal system in the bony plates, of tubular dentin, of external pores in the enamel layer and of a link to the lateral line system promoted hypotheses that the bony plates and tooth precursors may have had a sensory function. The evolution of an efficient brain, of a head with paired sense organs and of toothed jaws concurred with a shift from a sessile filter-feeding life to active prey hunting. (3) The wide spectrum of feeding behaviors exhibited by modern vertebrates is reflected by a variety of dentition types. While the teeth are continuously renewed in toothed non-mammalian vertebrates, tooth turnover is highly restricted in mammals. As a rule, one set of primary teeth is replaced by one set of permanent teeth. Since teeth are richly innervated, the turnover necessitates a local neural plasticity. Another factor calling for a local plasticity is the relatively frequent occurrence of age-related and pathological dental changes. (4) Tooth development is initiated through interactions between the oral epithelium and underlying neural crest-derived mesenchymal cells. The interactions are mediated by cell surface molecules, extracellular matrix molecules and soluble molecules. The possibility that the initiating events might involve a neural component has been much discussed. With respect to mammals, the experimental evidence available does not support this hypothesis. In the teleost Tilapia mariae, on the other hand, tooth germ formation is interrupted, and tooth turnover ceases after local denervation. (5) Prospective dental nerves enter the jaws well before onset of tooth development. When a dental lamina has formed, a plexus of nerve branches is seen in the subepithelial mesenchyme. Shortly thereafter, specific branches to individual tooth primordia can be distinguished. In bud stage tooth germs, axon terminals surround the condensed mesenchyme and in cap stage primordia axons grow into the dental follicle.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗