Proliferative effect of cannabidiol in human gingival fibroblasts via the mitogen-activated extracellular signal-regulated kinase (MEK) 1/2.

BACKGROUND AND OBJECTIVES: Cannabidiol exerts its anti-inflammatory and anti-oxidant activities in various human cells. However, its proliferative effect has not been extrapolated to human gingival fibroblasts (HGFs). This study aimed to determine the proliferative and promigratory effects of cannabidiol in HGFs and to elucidate the signaling mechanism(s). MATERIALS AND METHODS: HGFs, characterized by their CD73, CD90, and CD105 expressions by flow cytometry, were treated with cannabidiol at 0.01-30 µM. The cytotoxicity was determined by the MTT assay, while the proliferative effect was examined by the BrdU assay, immunoblot and immunofluorescence for cyclin D1 and Ki-67 expressions, respectively, and cell cycle analysis. The promigratory effect of cannabidiol was investigated by a wound healing assay. Phosphorylation of the p38 MAPK, JNK, and ERK upon treatment with cannabidiol was explored, and their involvement in cell proliferation and cyclin D1 and Ki-67 expressions was studied using pharmacological inhibitors. RESULTS: No toxicity was found in HGFs treated with any doses of cannabidiol up to 30 µM. The mean percentage of cell proliferation was significantly enhanced by treatment with cannabidiol at 3 or 10 µM (p < .001), consistent with upregulated expressions of cyclin D1 and Ki-67 and increased percentages of HGFs in the S and G2/M phases. Moreover, treatment with cannabidiol significantly induced cell migration (p < .05). The p38 MAPK and ERK1/2 were significantly activated by cannabidiol (p < .05), but only pretreatment with UO126, a MEK1/2 inhibitor, significantly inhibited cell proliferation and cyclin D1 and Ki-67 expressions (p < .05). CONCLUSION: Treatment with cannabidiol at non-toxic doses promotes HGFs' proliferation and migration.

Microcirculation and micromorphology of healthy and inflamed gingivae.

Inflammation changes the microcirculatory and micromorphological dynamics of human gingiva. Laser Doppler flowmetry (LDF) and a replica technique for scanning electron microscopy (SEM) were used to examine the facial soft tissues of six maxillary anterior teeth, before and after treatment, in 12 patients exhibiting clinically healthy tissues and in 12 others with moderate gingivitis. All patients received oral hygiene instructions and scaling. The gingiva in the gingivitis group became healthy within 3 months after treatment. LDF results were recorded at the free gingivae, interdental gingivae, attached gingivae, and alveolar mucosae of the six maxillary anterior teeth. The gingival blood flows in the gingivitis group before treatment were significantly different from those in the healthy gingiva group. Flows were restored to the same level as the healthy gingiva, with no significant difference, at P > 0.01, 3 months after treatment. However, there were significant differences among sites during the same period. In addition, blood flow was reduced to a normal level after the inflammation subsided. Initially, the gingival morphology of the inflamed sites exhibited irregular free gingival margins, in contrast to that of healthy gingivae, which were characterized by rounded margins closely adapted to the tooth. One month post-treatment, the gingivae exhibited a wrinkled appearance, but they had reverted to normal micromorphology by 3 months post-treatment. The replica impression technique can be used to record gingival micromorphology both before and after reduction of inflammation.

Effect of triclosan on healing following non-surgical periodontal therapy in smokers.

BACKGROUND: Tobacco smoking is an established risk factor for periodontitis, and is associated with periodontal attachment and tooth loss. Clinical studies have indicated that smoking may adversely affect and impede healing following periodontal therapy. Adjunctive antimicrobials, on the other hand, have been shown to enhance the effect of non-surgical periodontal therapy. The objective of this study was to evaluate the effect of a triclosan/copolymer/fluoride dentifrice on healing following non-surgical periodontal therapy in smokers. METHODS: Sixty smokers (aged 35-59 years; 23 females) with chronic periodontal disease volunteered to participate in a double-blind, randomized, controlled, clinical trial. The subjects were randomly assigned to use a triclosan/copolymer/fluoride (30 subjects) or a standard fluoride (30 subjects) dentifrice and received detailed information on proper techniques for self-performed plaque control. The participants then received non-surgical periodontal therapy followed by periodontal maintenance care every 6 months over 24 months. Clinical recordings included evaluation of oral hygiene standards, gingival health, and periodontal status. RESULTS: Subjects using the triclosan/copolymer/fluoride dentifrice exhibited significantly improved oral hygiene conditions, gingival health, and periodontal status compared with those using the standard fluoride dentifrice over the 24-month maintenance interval. CONCLUSIONS: The results suggest that an oral hygiene regimen including a triclosan/copolymer/fluoride dentifrice may sustain the short-term effect of non-surgical periodontal therapy in smokers.

Prevalence and severity of periodontal disease at mandibular molar teeth in smokers with regular oral hygiene habits.

BACKGROUND: Smoking appears to be detrimental to health because it has been associated with several diseases including cancer and cardiovascular diseases. Smoking also appears to be a major environmental factor associated with periodontal disease progression. The objective of this study was to evaluate the prevalence and severity of periodontal destruction as influenced by smoking in a Thai population. METHODS: Gingival health and periodontal conditions at mandibular molar furcation sites in 120 Thai dental patients (60 smokers and 60 never-smokers, age range 31 to 60 years) with generally high oral hygiene standards and regular dental care habits were evaluated. RESULTS: Smokers exhibited more frequent and severe mandibular molar periodontal destruction than never-smokers. The prevalence and severity of gingival recession, periodontal pocket formation, clinical attachment loss, furcation involvement, and tooth mobility were significantly increased in smokers compared to never-smokers. Seventy-three percent of the smokers exhibited furcation involvement in contrast to only 20% of the never-smokers. CONCLUSIONS: The results of this study suggest that smoking appears to be a major environmental factor associated with accelerated periodontal destruction in adult smokers with generally high oral hygiene standards and regular dental care habits in a Thai population.

Microcirculation of the healthy human gingiva.

The purpose of this study was to evaluate the microcirculation in healthy human gingiva. Forty-two adult volunteers with clinically healthy gingiva participated. The ages of this research sample ranged from 20 to 30 years. Periodontal conditions were evaluated and assessed by using the qualitative plaque index, gingival index, gingival bleeding index, tooth mobility, and laser Doppler flow-metry (LDF) on 12 maxillary and mandibular anterior teeth. The LDF data were recorded on the facial aspect of the free gingiva, interdental gingiva, attached gingiva, and alveolar mucosa of 12 maxillary and mandibular anterior teeth, utilizing an acrylic stent to stabilize the probe. This technique was then modified to circumvent contamination by saliva and gingival exudate. Blood flow in the maxillary anterior gingiva differed significantly from that in the mandibular anterior gingiva in interdental gingiva, attached gingiva, and alveolar mucosa, at P< 0.01. The maxillary anterior gingiva, at each point on the stent, showed significant differences in the mean LDF, at P< 0.01. For the mandibular anterior gingiva, the difference was significant only in the alveolar mucosa region.

Blood flow and human periodontal status.

The purpose of this study was to evaluate the microcirculation in subjects with moderate gingivitis, periodontitis, and healthy gingiva. Sixty adult volunteers with clinically healthy gingiva, moderate gingivitis, and periodontitis (20 subjects each) participated in this study. The ages of the research samples ranged from 20 to 35 years. Gingival health was evaluated by using the qualitative plaque index, gingival index, gingival bleeding index, tooth mobility, probing pocket depth, clinical attachment level, and laser Doppler flowmetry (LDF) on six maxillary anterior teeth. LDF data were recorded at the facial aspect of free gingivae, interdental gingivae, attached gingivae, and alveolar mucosae on six maxillary anterior teeth, utilizing an acrylic stent to stabilize the probe. This technique was then modified to circumvent contamination by saliva and gingival exudate. When results were compared at similar sites in each patient within a trial group, there were significant differences in blood flow measurements at all the sites examined between moderate gingivitis and periodontitis when compared with measurements in healthy human gingiva. However, blood flow measurements within the same group showed significant differences at every site, at P< 0.01.