Bone Morphogenetic Proteins (BMPs) form a unique group of proteins within the Transforming Growth Factor beta (TGF-β) superfamily of genes and have pivotal roles in the regulation of bone induction, maintenance and repair. They act through an autocrine or paracrine mechanism by binding to cell surface receptors and initiating a sequence of downstream events that have effects on various cell types. Differentiation of osteoprogenitor mesenchymal cells and up-regulation of osteoblastic features occur under the influence of cytokines and growth factors that are expressed with the direct or indirect guidance of BMPs acting at the transcriptional level or higher. The Smads family of proteins has been identified as the downstream propagator of BMP signals, whereas hedgehog genes are possible modulators of BMP expression. The inflammatory response observed during wound repair and fracture healing, results in by-products that interact with BMPs and affect their biologic potential. Additive, negative or synergistic effects are observed when homodimeric or heterodimeric forms of BMPs interact with BMP receptors. Storage within the bone matrix allows for their involvement in the modeling/remodeling process by mediating coupling of osteoblasts and osteoclasts. Micro-environmental conditions, dose, possible carrier materials and geometrical parameters of delivery matrix are critical determinants of the pharmacokinetics of BMP action and the biologic outcome during wound repair. Because of their osteogenic potential, BMPs are of tremendous interest as therapeutic agents for healing fractures of bones, preventing osteoporosis, treating periodontal defects and enhancing bone formation around alloplastic materials implanted in bone. (J. Oral Sci. 45, 57-73, 2003)

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Dopamine receptor function in spontaneously hypertensive rats (SHR) and in control progenitor Wistar-Kyoto (WKY) rats was assessed from their dopamine D₁-like/D₂-like receptor-mediated jaw movements and dopamine release from the nucleus accumbens and from the ventrolateral striatum measured by an in vivo microdialysis technique. Spontaneous locomotor activity and rearing were significantly higher in SHR than in WKY rats. Coadministration of SKF 38393 (1.0, 2.0 and 3.0 mg/kg), a dopamine D₁-like receptor agonist, and quinpirole (1.0 mg/kg), a dopamine D₂-like receptor agonist, produced repetitive jaw movements in WKY rats in a dosedependent manner. However, this synergism was not evident in SHR. Basal dopamine levels in both the nucleus accumbens and the ventrolateral striatum were lower in SHR than WKY rats, though the levels of dopamine were lower in the nucleus accumbens than the ventrolateral striatum in both strains. After infusion of quinpirole (100 μM for 180 min) the dopamine levels in both regions were reduced. In the nucleus accumbens, the quinpirole-mediated reduction of dopamine release at 40 min and 60 min after infusion was larger in SHR than WKY rats, whereas this difference between the SHR and WKY rats was small in the ventrolateral striatum. The present study therefore suggests that, when compared to WKY rats, postsynaptic dopamine D₁-like/D₂-like receptors in the SHR are hyposensitive, while presynaptic dopamine D₂-like receptors located particularly in the nucleus accumbens are hypersensitive. (J. Oral Sci. 45, 75-83, 2003)

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The presence of hyaluronan (HA), hyaluronidase and hyaluronidase inhibitors has been assayed in pure resting and stimulated parotid saliva and also in resting and stimulated mixed saliva utilizing an ELISA-type assay and its modifications. Results confirmed the presence of hyaluronan in all saliva specimens which generally decreased upon stimulation. Hyaluronan in parotid saliva was of high molecular weight (> 200, 000 kDa) whilst that in whole saliva in the floor of the mouth had a molecular weight between 20, 000 kDa and 200, 000 kDa, presumably because of cleavage by bacterial hyaluronidases. Hyaluronidase detection was variable in saliva, being present in some specimens of unstimulated parotid saliva, but in fewer specimens of stimulated saliva. Hyaluronidase was detected in parotid and whole saliva, both in the resting and stimulated state, at pH 3.7. Unstimulated whole saliva also showed hyaluronidase activity at pH 6.8, suggesting a different origin for this hyaluronidase. Hyaluronidase inhibitors were identified in both parotid and mixed whole saliva. There was an inverse relationship between the presence of hyaluranidase and the presence of hyluronidase inhibitors, suggesting a feedback mechanism. The possible significance, interactions and function of hyaluronan, hyaluronidase and its regulation by hyaluronidase inhibitors in saliva is discussed, particularly in relation to intra-oral wound healing and periodontal disease. (J. Oral Sci. 45, 85-91, 2003)

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The aim of this study was to assess whether a clinical evaluation of oral cleanliness reflects subsequent caries incidence. Oral examination of 180 children (1-to 4-year-olds) was carried out twice in a six-month period. Caries prevalence at baseline (dfs) in 1-to 2-year-olds (group A) and 3-to 4-year-olds (group B) correlated significantly with oral cleanliness as well as salivary mutans streptococci count (MS). Caries increment (Δdfs) correlated significantly with oral cleanliness in group A but not in group B, whileΔdfs significantly correlated with MS in group B and slightly correlated with that in group A. ANCOVA revealed that dfs was significantly higher at the second examination than at baseline in group B, even after adjusting for oral cleanliness. This finding was confirmed by Wilcoxon test when group B was divided in three categories (low, middle and high) based on oral cleanliness. This suggests that the relationship betweenΔdfs and oral cleanliness decreased with age and that the significant positive correlation found in group B by our point-prevalence survey is derived from the remainder of the positive correlation that occurred at a younger age. (J. Oral Sci. 45, 93-98, 2003)

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Large quantities of Prevotella nigrescens ATCC 25261 (P. nigrescens) cells adhere to hydroxyapatite (HA) treated with extract from Porphyromonas gingivalis 381 (Pg-Ext), but not to HA coated with human serum albumin (HSA) or human serum globulin (HSG). The duration of HA treatment with Pg-Ext and several other conditions were tested to determine the factors causing Pg-Ext to promote P. nigrescens cell adhesion. Pg-Ext adsorbed rapidly to HA in less than 5 min. The maximum adherence of P. nigrescens cells to HA was observed after treatment of HSA and HSG and then retreatment of HA with Pg-Ext. It was found that Pg-Ext heated at 80°C for 30 min did not lose its propensity to promote attachment of P. nigrescens to HA and that it also remained stable at 4°C for at least 6 days. The trypsin-like enzyme activity of Pg-Ext was also measured, with BAPNA as the substrate and commercially purchased trypsin as the standard, and was approximately 0.12 units/mg. These data suggest that the presence of Pg-Ext is one of the essential factors responsible for P. nigrescens cell attachment to apatitic surfaces, and that with its trypsin-like activity, Pg-Ext may be considered an extremely important substance for the establishment of P. nigrescens in the periodontal pocket and the development of periodontal disease. (J. Oral Sci. 45, 99-106, 2003)

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Recurrent aphthous ulceration (RAU) is the most common lesion of the oral mucosa. Although many factors have been postulated as etiological factors for RAU, the role of Helicobacter pylori as a causative agent of RAU remains controversial. We therefore investigated the association of H. pylori and RAU by a highly sensitive technique, nested polymerase chain reaction (PCR), in 22 patients with RAU with ages ranging from 12-36 years. Samples were brushed from the lesions and the dorsum of the tongue of each patient. In addition, samples from the dorsum of the tongue of 15 normal individuals with ages ranging from 13-40 years were used as controls. The results showed that only one sample from a lesion (4.5 %) and one sample from the tongue (4.5 %) of two different patients with RAU were positive for H. pylori. In the control group, 3 samples (20 %) were positive for H. pylori. These findings suggest that H. pylori does not play a role in the pathogenesis of RAU and the dorsum of the tongue may be a reservoir of H. pylori in some individuals. (J. Oral Sci. 45, 107-110, 2003)

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Porphyromonas gingivalis has been implicated as a major pathogen in periodontal diseases. We previously cloned a 40-kDa outer membrane protein (OMP) gene from P. gingivalis 381 and succeeded in producing sufficient quantities of the recombinant protein for experimental use. Since antibodies against the recombinant (r) 40-kDa OMP have potent ability to kill P. gingivalis cells by complement activation and opsonization, r40-kDa OMP has been the subject of considerable interest as a possible vaccine candidate. In this study, in order to develop a component vaccine, the immunodominant domain in 40-kDa OMP was identified. Peptides corresponding to portions of the N-terminal regions of 40-kDa OMP were synthesized chemically and their immunoreactivities with antibody against r40-kDa OMP were tested. The 16-mer peptide, LDDEYKERVFQTFVHY, was found to react strongly with the antibody. Furthermore, a rabbit antibody was prepared by immunization with the 16-mer peptide, cross-linked with dehydrofolate reductase, and its immunoreactivity was then examined. In a BIAcore experiment the antibody clearly reacted with r40-kDa OMP as well as P. gingivalis strains. These findings suggest that the 16-mer synthetic peptide may be useful for development of a component vaccine against P. gingivalis. (J. Oral Sci. 45, 111-116, 2003)

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Oral findings in a case of Noonan syndrome in an 8-year-old Japanese male are reported. Examination of the patient revealed a narrow, high-arched palate and an anterior open bite. Cephalometric measurements showed a wide gonial angle, a large mandibular plane angle, a large Y-axis and long facial height. It is suggested that the patient had a skeletal open-bite malocclusion, which included an abnormal swallowing habit. (J. Oral Sci. 45, 117-121, 2003)

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