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MicroRNAs (miRNAs) are a group of small RNAs that control gene expression in all aspects of eukaryotic life, primarily through RNA silencing mechanisms. The purpose of the present review is to introduce key miRNAs involved in periodontal homeostasis, summarize the mechanisms by which they affect downstream genes and tissues, and provide an introduction into the therapeutic potential of periodontal miRNAs. In general, miRNAs function synergistically to fine-tune the regulation of biological processes and to remove expression noise rather than by causing drastic changes in expression levels. In the periodontium, miRNAs play key roles in development and periodontal homeostasis and during the loss of periodontal tissue integrity as a result of periodontal disease. As part of the anabolic phase of periodontal homeostasis and periodontal development, miRNAs direct periodontal fibroblasts toward alveolar bone lineage differentiation and new bone formation through WNT, bone morphogenetic protein, and Notch signaling pathways. miRNAs contribute equally to the catabolic aspect of periodontal homeostasis as they affect osteoclastogenesis and osteoclast function, either by directly promoting osteoclast activity or by inhibiting osteoclast signaling intermediaries or through negative feedback loops. Their small size and ability to target multiple regulatory networks of related sets of genes have predisposed miRNAs to become ideal candidates for drug delivery and tissue regeneration. To address the immense therapeutic potential of miRNAs and their antagomirs, an ever growing number of delivery approaches toward clinical applications have been developed, including nanoparticle carriers and secondary structure interference inhibitor systems. However, only a fraction of the miRNAs involved in periodontal health and disease are known today. It is anticipated that continued research will lead to a more comprehensive understanding of the periodontal miRNA world, and a systematic effort toward harnessing the enormous therapeutic potential of these small molecules will greatly benefit the future of periodontal patient care.

The aim of the present critical review is to summarize recent evidence on the prevalence of peri-implant diseases and their similarities and differences with periodontal diseases with a focus on their pathogenetic mechanisms. Reports on the extent and severity of peri-implant diseases are influenced by different case definitions. The prevalence of peri-implant diseases is reported at the subject or implant level and affected by the type of population samples analyzed (e.g., randomly selected population samples or convenience samples). The outcomes of studies on animals and humans indicate that experimental biofilm accumulation leads to a higher frequency of bleeding sites around implants as compared with teeth. Despite the proof of principle that experimentally induced mucositis may be reversible, early diagnosis and management of naturally occurring peri-implant mucositis are clinically relevant. Tissue destruction at experimental peri-implantitis sites is faster and more extensive when compared with that at experimental periodontitis sites. Although human periodontitis and peri-implantitis lesions share similarities with respect to etiology and clinical features, they represent distinct entities from a histopathologic point of view. To avoid implant loss, patients diagnosed with peri-implantitis should be treated without delay.

Lymphatic vessels return extravasated fluid, proteins, and cells back into the circulation and are important in immune cell trafficking. In the gingiva, lymphatic vessels are located in the lamina propria and travel over the external surface of the alveolar bone. The gingival lymphatics are important for fluid drainage, since lack of lymphatics has been shown to increase interstitial fluid pressure and fluid volume. Maintenance of gingival lymphatic vessels requires continuous signaling by the growth factors VEGF-C and -D via their receptor VEGFR-3. The growth factors are expressed in the gingival epithelium and also in immune cells in the lamina propria. VEGF-C seems to be crucial for lymphangiogenesis induced during periodontal disease development. The lymphatic vessels protect against periodontitis in mice, probably by clearing bacteria and bacterial products and by promoting humoral immune responses. Down-regulation of CCL21, a ligand important for dendritic cell migration, has been demonstrated in lymphatics from patients with periodontitis. High enzymatic activity in the gingiva of these patients may also contribute to impaired lymphatic function, due to the loss of structural components in the interstitium influencing lymphatic function. So far, knowledge is limited in this field because of the dearth of studies on the role of lymphatic vessels in periodontal disease.

The influence of alveolar bone support on the functional capability of a tooth remains unclear. It was hypothesized that a reduction in alveolar support causes an increase of maximum stress in the periodontal structures. Mathematical models of the maxillary incisor to simulate in vivo tooth movement were constructed with periodontium of normal or reduced bone height, and normal or widened periodontal ligament (PDL) space. Under simulated bite force, the maximum tensile stress at the lingual cervical region in the PDL increased with bone height reduction, but decreased with PDL widening. The compressive stress at the cervical region in the cortical bone was no more than 22% of the yield strength of bone, and did not increase by the height reduction with widened PDL. The result suggests that the height reduction potentially causes mechanical damage to the PDL, but, of itself, is not likely to have a negative effect on the bone.

Diabetes, particularly type 2 diabetes, is a looming health issue with many ramifications. Because diabetes alters the cellular microenvironment in many different types of tissues, it causes myriad untoward effects, collectively referred to as 'diabetic complications'. Two cellular processes affected by diabetes are inflammation and apoptosis. This review discusses how diabetes-enhanced inflammation and apoptosis may affect the oral environment. In particular, dysregulation of tumor necrosis factor and the formation of advanced glycation products, both of which occur at higher levels in diabetic humans and animal models, potentiate inflammatory responses and induce apoptosis of matrix-producing cells. The enhanced loss of fibroblasts and osteoblasts through apoptosis in diabetics could contribute to limited repair of injured tissue, particularly when combined with other known deficits in diabetic wound-healing. These findings may shed light on diabetes-enhanced risk of periodontal diseases.

Previously, burst and linear theories for periodontal disease progression were proposed based on different but limited statistical methods of analysis. Multilevel modeling provides a new approach, yielding a more comprehensive model. Random coefficient models were used to analyze longitudinal periodontal data consisting of repeated measures (level 1), sites (level 2), teeth (level 3), and subjects (level 4). Large negative and highly significant correlations between random linear and quadratic time coefficients indicated that subjects and teeth with greater-than-average linear change experienced decelerated variation. Conversely, subjects and teeth with less-than-average linear change experienced accelerated variation. Change therefore exhibited a dynamic regression to the mean at the tooth and subject levels. Since no equilibrium was attained throughout the study, changes were cyclical. When considered as a multilevel system, the "linear" and "burst" theories of periodontal disease progression are a manifestation of the same phenomenon: Some sites improve while others progress, in a cyclical manner.

P. gingivalis is an important oral pathogen, which has been closely linked to periodontal disease as well as lesions of endodontic origin. Both infections are associated with a decrease in fibroblast numbers, formation of an inflammatory infiltrate, and bone resorption. The goal of this study was to investigate the role that the host response plays in the capacity of P. gingivalis to stimulate fibroblast apoptosis, PMN recruitment, and osteoclastogenesis. This was accomplished by the use of an in vivo calvarial model in mice with targeted deletion of TNF receptors p55 and p75 and matched wild-type mice. The results indicate that P. gingivalis induces fibroblast apoptosis in vivo and establish for the first time that this involves the stimulation of a host response. Moreover, bacteria-stimulated PMN recruitment and osteoclastogenesis were also dependent upon the host response. The results suggest that much of the damage caused by P. gingivalis infection, including fibroblast apoptosis, at least under some circumstances, results from stimulation of the host response rather than the direct effect of bacterial products. Furthermore, this may represent a more general mechanism by which bacterial challenge induces apoptosis of matrix-producing cells through the induction of TNF.

Forty-one subjects with bad breath were assessed for oral malodor and periodontal status on three occasions, at intervals of approximately one week. Oral malodor was assessed by measurement of peak and steady-state volatile sulphide levels with a portable sulphide monitor and by organoleptic measurement of whole-mouth, tongue dorsum, and interproximal dental odors by two independent judges. Reproducibility of measurements, assessed by paired t tests and Kappa testing, demonstrated no significant differences between any of the test results from the first and second appointments. Steady-state sulphide levels were the most reproducible of all tests. The ability of the tests to detect an expected reduction of malodor following a 0.2% chlorhexidine mouthrinse regimen was investigated by comparison of test values between the second and third appointments. Following the mouthrinsing treatment, 43% reductions of peak, 47% reductions of steady-state volatile sulphide levels, and 15-58% reductions in all other measurement categories were observed. The majority of the participants (22/41) had no pockets greater than 5 mm and exhibited both moderate gingival inflammation (Mean Gingival Index = 1.17) and moderate plaque accumulation (Mean Plaque Index = 1.84). Plaque Index and presence of pockets greater than 7 mm were weakly related to sulphide measurements. Whereas assessment of steady-state sulphide levels by the sulphide monitor does not constitute a direct measure of oral malodor, its relation to organoleptic measurement, superior reproducibility, objectivity, and sensitivity support the use of the sulphide monitor in clinical studies.

The purpose of this epidemiological study was to estimate the degree of change in periodontal attachment level in a sample of adults examined in 1959 and 1987 in Tecumseh, Michigan. Out of 526 individuals between the ages of five and 60 years in 1959, a sample of 325 resided within an 80-km-radius area in 1987. Of those, 167 were re-examined. Loss of periodontal attachment (LPA) was determined with a Michigan #0 probe on four tooth sites (disto-buccal, mid-buccal, mesio-buccal, mid-lingual) for all teeth present. Of the individuals contacted, 28 had lost all their teeth during the 28 years. Of the 167 adults examined, two refused periodontal probing. Out of the 165 adults with LPA measurements in 1987, only 22 (13.3%) had an average increased loss of 2 mm or more per person between 1959 and 1987; five adults (3.0%) had an average LPA increase of 3 mm or more, and only two adults (1.2%) had an average LPA increase of 4 mm or more. The attachment level in 59.3% of all the tooth sites examined in 1959 in the 165 individuals either did not change or changed within +/- 1.0 mm. On the basis of bivariate analyses, the individuals with high LPA increase (greater than or equal to 2 mm) had the following characteristics significantly different from those with low LPA increase: They were older, smoked, had tooth mobility at baseline, higher gingivitis, plaque, calculus, and tooth mobility scores at follow-up, lower education level, and irregular dental attendance.(ABSTRACT TRUNCATED AT 250 WORDS)

Protease activity was measured in dental plaque collected from patients with or without supragingival calculus. Plaque specimens from the calculus group showed significantly greater protease activity in the presence of 0.05% sodium thioglycollate than did those from the non-calculus group. No significant difference between the two groups was observed in the protease activity without sodium thioglycollate. There was no significant correlation between the age of the patients and the protease activity.

Most of the participants agreed that the destruction of connective tissue is the single most significant criterion for assessing the severity of periodontal disease. Members were equally divided between favoring a measure of bone height or density and a measure of soft tissue destruction, such as attachment level or pocket depth. A measure of the rate of destruction of bone at the time of examination was considered to be especially useful. Opinion was equally divided as to the second most important parameter related to periodontal disease, either measures of gingival inflammation or measures of dental plaque. Measurements of gingival fluid and measures of tooth mobility were less favored by the group as a whole, but each measurement area was favored by strong proponents.

Two antimicrobial agents, 9-aminoacridine (0.2%) and minocycline (0.2%), were evaluated for their efficacy in inhibiting root surface caries, bone loss, and microflora in rice rats. A solution of 5000 ppm fluoride was used as a positive control for the inhibition of root surface caries, and double-distilled water was used as a negative control group. Each rat was treated by having its molar teeth swabbed 2 X per day with the prescribed agent in its group for nine weeks. Root caries reduction in the minocycline and fluoride groups was not significantly different, but the reduction was significantly greater than in the 9-aminoacridine group, with the caries score in all three groups being significantly less than that in the water control. Bone loss reduction for the minocycline group was significantly greater than that for any other group.

Dentin stresses from simulated functional loads to post-reinforced tooth models with four levels of periodontal support were calculated using finite element analysis. As bone levels diminished, stresses were found to increase dramatically and to concentrate in the small amount of dentin remaining near the post apex.