Lipase-a single-nucleotide polymorphism rs143793106 is associated with increased risk of aggressive periodontitis by negative influence on the cytodifferentiation of human periodontal ligament cells.

BACKGROUND AND OBJECTIVE: Aggressive periodontitis (AgP) is characterized by general health and rapid destruction of periodontal tissue. The familial aggregation of this disease highlights the involvement of genetic factors in its pathogeny. We conducted a genome-wide association study (GWAS) to identify AgP-related genes in a Japanese population, and the lipid metabolism-related gene, lipase-a, lysosomal acid type (LIPA), was suggested as an AgP candidate gene. However, there is no report about the expression and function(s) of LIPA in periodontal tissue. Hence, we studied the involvement of how LIPA and its single-nucleotide polymorphism (SNP) rs143793106 in AgP by functional analyses of LIPA and its SNP in human periodontal ligament (HPDL) cells. MATERIALS AND METHODS: GWAS was performed using the genome database of Japanese AgP patients, and the GWAS result was confirmed using Sanger sequencing. We examined the mRNA expression level of LIPA and the protein expression level of the encoded protein lysosomal acid lipase (LAL) in periodontium-composing cells using conventional and real-time polymerase chain reaction (PCR) and western blotting, respectively. Lentiviral vectors expressing LIPA wild-type (LIPA WT) and LIPA SNP rs143793106 (LIPA mut) were transfected into HPDL cells. Western blotting was performed to confirm the transfection. LAL activity of transfected HPDL cells was determined using the lysosomal acid lipase activity assay. Transfected HPDL cells were cultured in mineralization medium. During the cytodifferentiation of transfected HPDL cells, mRNA expression of calcification-related genes, alkaline phosphatase (ALPase) activity and calcified nodule formation were assessed using real-time PCR, ALPase assay, and alizarin red staining, respectively. RESULTS: The GWAS study identified 11 AgP-related candidate genes, including LIPA SNP rs143793106. The minor allele frequency of LIPA SNP rs143793106 in AgP patients was higher than that in healthy subjects. LIPA mRNA and LAL protein were expressed in HPDL cells; furthermore, they upregulated the cytodifferentiation of HPDL cells. LAL activity was lower in LIPA SNP-transfected HPDL cells during cytodifferentiation than that in LIPA WT-transfected HPDL cells. In addition, ALPase activity, calcified nodule formation, and calcification-related gene expression levels were lower during cytodifferentiation in LIPA SNP-transfected HPDL cells than those in LIPA WT-transfected HPDL cells. CONCLUSION: LIPA, identified as an AgP-related gene in a Japanese population, is expressed in HPDL cells and is involved in regulating cytodifferentiation of HPDL cells. LIPA SNP rs143793106 suppressed cytodifferentiation of HPDL cells by decreasing LAL activity, thereby contributing to the development of AgP.

Relationship between health literacy and physical function of patients participating in phase I cardiac rehabilitation: a multicenter clinical study.

Health literacy (HL) is an important decision factor for health. Both low HL and low physical function cause adverse events in cardiovascular disease patients, but their relationship is not well documented. To clarify the relationship between HL and physical function of patients participating in cardiac rehabilitation and calculate the cutoff value of the 14-item HL scale (HLS) for low handgrip strength, this multicenter clinical study named the Kobe-Cardiac Rehabilitation project for people around the World (K-CREW) was conducted among four affiliated hospitals with patients who underwent cardiac rehabilitation. We used the 14-item HLS to assess HL, and the main outcomes were handgrip strength and Short Physical Performance Battery (SPPB) score. The study included 167 cardiac rehabilitation patients with a mean age of 70.5 ± 12.8 years, and the ratio of males was 74%. Among them, 90 patients (53.9%) had low HL and scored significantly lower in both handgrip strength and SPPB. Multiple linear regression analysis revealed that HL was a determinant factor (ß = 0.118, p = 0.04) for handgrip strength. Receiver operating characteristic analysis revealed the cutoff value of the 14-item HLS for screening for low handgrip strength was 47.0 points, and the area under the curve was 0.73. This study showed that HL was significantly associated with handgrip strength and SPPB in cardiac rehabilitation patients and suggests the possibility of early screening for low HL to improve physical function in cardiac rehabilitation patients with low HL.

The significance of information and communication technology education via tablets in college of physical therapy.

[Purpose] This study aimed to clarify whether collaborative learning could be promoted via information and communication technology education using tablets at college of physical therapy. [Participants and Methods] An online survey was conducted to evaluate collaborative learning among 81 first-year students at the Department of Physical Therapy actively using tablets in classes (six specific categories). [Results] The Friedman test had significant results, and a significant primary effect was observed between each questionnaire item. Following this, the Bonferroni test was performed for multiple comparisons, with significant differences were observed among certain items. [Conclusion] We reported employing tablets in the classroom positively impacted collaborative learning. Here, among the evaluations of collaborative learning, the items with the best results corresponded mainly to communication activation between students.

A zirconia-based column chromatography system optimized for the purification of IgM from hybridoma culture supernatants.

By using EDTPA-modified zirconia particles that selectively adsorb immunoglobulins in a column, we developed a chromatography separation system for efficient concentrating and purifying of IgM from hybridoma culture supernatants. Hybridoma culture supernatants containing IgMs were diluted 3-fold with 10 mM phosphate buffer (pH 7.0) and passed through the column. During this process, zirconia particles selectively adsorbed these IgMs, and most of the contaminating proteins flowed out into the flow-through. The adsorbed IgMs were easily eluted with a small volume of 400 mM phosphate buffer (pH 8.0), and high-concentration IgM solutions were prepared. Subsequent simple processing using a Capto™ Core 400 cartridge column provided highly purified IgM. The operation is easy, and the activity of IgM is maintained because the purification process is performed using only neutral ranges of phosphate buffers. Here, we showed that anti-globoside and anti-CDw75 IgM purified by this method can be used to stain cervical cancer and Burkitt lymphoma cells that specifically express these respective tumor-associated carbohydrate antigens.

Interactions between Amino Acids and Zirconia Modified with Ethylenediaminetetra(methylenephosphonic acid): Mechanistic Insights into the Selective Binding of Antibodies.

Zirconia modified with ethylenediaminetetra(methylenephosphonic acid) (EDTMP) has an affinity for antibodies, including immunoglobulin G (IgG) and immunoglobulin M (IgM). However, little is known about the mechanism underlying antibody selectivity. In this study, we examined the interactions of EDTMP-modified zirconia with proteinogenic amino acids using chromatographic and batch methods to gain mechanistic insights into antibody selectivity at the amino acid level. We demonstrated that EDTMP-modified zirconia has an affinity for amino acids with a positively charged side chain, especially lysine. Similar trends were observed for oligopeptides. This affinity was reduced by the addition of sodium phosphate or sodium polyphosphates. Thus, the antibody selectivity of EDTMP-modified zirconia is primarily ascribable to electrostatic attractions between the EDTMP moieties of the zirconia surfaces and the constant region of antibodies that are rich in lysine residues. Consistent with this, the human IgG antibody has a higher adsorption ability onto EDTMP-modified zirconia than the rabbit IgG antibody, which has fewer lysine residues in the constant region. These findings are useful not only for improving antibody purification but also for developing new applications, including purification of proteins tagged with positively charged amino acid residues.

Aromatase inhibitor anastrozole modifies cellular functions in gingival fibroblasts and endothelial cells: possible periodontal complications of aromatase inhibitor treatment.

BACKGROUND: Recent studies have shown that treatment with aromatase inhibitors contributes to an increased prevalence of periodontitis. OBJECTIVE: In this study, we assessed effects of the aromatase inhibitor anastrozole on cellular function of human gingival fibroblasts (HGFs) and endothelial cells. METHODS: Expression levels of collagen, extracellular matrix (ECM) proteins, matrix metalloproteinases (MMPs), and tissue inhibitors of metalloproteinases (TIMPs) were examined in HGFs exposed to anastrozole. Furthermore, inflammatory responses in HGFs cultured with anastrozole were evaluated in the presence of Porphyromonas gingivalis lipopolysaccharide. We also evaluated the vascular permeability and vascular endothelial (VE)-cadherin expression of endothelial cells exposed to anastrozole. RESULTS: Anastrozole enhanced expression levels of collagen, ECM proteins, TIMPs, and inflammatory cytokines in HGFs, as well as vascular permeability of endothelial cells. In addition, anastrozole reduced expression levels of MMPs in HGFs and VE-cadherin in endothelial cells. CONCLUSION: These results suggest that anastrozole modulates various cellular functions in HGFs and endothelial cells.

Long-term exposure to cigarette smoke influences characteristics in human gingival fibroblasts.

BACKGROUND: Periodontal disease is a chronic inflammatory disease caused by periodontopathic bacteria accumulated in the gingival sulcus and periodontal pocket. Cigarette smoking is a well-established risk factor for periodontal disease, and periodontal tissues in smokers are chronically exposed to cigarette smoke on a long-term basis. OBJECTIVE: In this study, we investigated the effects of long-term exposure to nicotine or cigarette smoke condensate (CSC) on cellular functions of human gingival fibroblasts (HGFs). METHODS: In vitro-maintained HGFs were divided into two groups. The HGFs of the short-term and the long-term culture groups were cultured for 4 and 25 days, respectively, in the presence or absence of nicotine, which is one of the main components of cigarette smoke, or CSC. The cellular proliferation and migration capacities of HGFs exposed to nicotine or CSC were evaluated by WST-1 and wound healing assays. The effects of exposure to nicotine or CSC on the expression of various extracellular matrix (ECM) components, inflammatory cytokines, and senescence-related genes were examined by real-time polymerase chain reaction and enzyme-linked immunosorbent assay. The cellular senescence of HGFs exposed to nicotine or CSC was detected by the senescence-associated ß-galactosidase (SA-ß-gal) assay. To explore the senescence-associated microRNA (miRNA), we extracted miRNA from the HGFs and the expression profiles were examined by miRNA array. RESULTS: In short-term culture, no significant changes were observed. Long-term exposure of HGFs to nicotine or CSC significantly suppressed their cellular proliferation and migration and upregulated type Ⅰ collagen, type Ⅲ collagen, interleukin (IL)-6, IL-8, p16, p21, and p53 mRNA expression, and IL-6 and IL-8 protein expression. Furthermore, long-term nicotine or CSC exposure significantly increased the percentage of SA-ß-gal-positive HGFs. In addition, long-term nicotine or CSC exposure reduced miR-29b and miR-199a expression to less than 50% of that in the unstimulated HGFs. CONCLUSION: These data suggest that long-term smoking habits may reduce wound healing ability, modulate ECM protein homeostasis, stimulate the inflammatory response, and accelerate cellular senescence in HGFs, and consequently accelerate the progression of periodontal diseases.

Predictors of activities of daily living at discharge in elderly patients with heart failure with preserved ejection fraction.

The purpose of this study was to clarify the predictive factors of activities of daily living (ADL) at discharge in elderly patients with heart failure with preserved ejection fraction (HFpEF). Participants were selected from among 598 consecutive hospitalized HF patients based on certain criteria. We investigated patient characteristics, and ADL with the motor and cognitive items of the Functional Independence Measure (FIM). We analyzed the data with the unpaired t test, Mann-Whitney U test, χ2 test, logistic regression analysis, and receiver operating characteristic (ROC) curves. We included 154 patients for further analyses who were divided into the low ADL group (n = 75) and high ADL group (n = 79). There were significant differences between the two groups in age, long-term care insurance (LTCI) level, New York Heart Association class, creatinine level, albumin level, ß-blocker, sitting, standing and walking exercise start days, length of hospital stay, and motor- and cognitive-FIM scores at admission and discharge (p < 0.05). The cutoff values of the ROC curves predicting ADL at discharge were LTCL: support level 2 (area under the curve [AUC]: 0.672, p < 0.001, sensitivity: 0.573, false-positive rate: 0.278); walking exercise start day: 4.5 days (AUC 0.694, p < 0.001, sensitivity: 0.609, false-positive rate: 0.299); motor FIM score: 34.5 points (AUC 0.710, p < 0.001, sensitivity: 0.633, false-positive rate: 0.280); and cognitive FIM score: 28.5 points (AUC 0.806, p < 0.001, sensitivity: 0.759, false-positive rate: 0.227). This study revealed several predictors of ADL at discharge and their associated cutoff values in elderly patients with HFpEF.

Gait speed, life-space mobility and mild cognitive impairment in patients with coronary artery disease.

Slow gait speed and restricted life-space mobility predict cognitive decline and dementia in healthy older adults, yet the relation between gait speed or life-space mobility and cognitive function remains poorly understood in patients with coronary artery disease (CAD). We, therefore, examined the following relations: that between gait speed and cognitive function, and mild cognitive impairment (MCI) and that between life-space mobility and cognitive function, and MCI. We conducted a cross-sectional study of 240 non-dementia patients who met the study criteria from 2132 consecutive CAD patients. MCI was estimated with the Japanese version of the Montreal Cognitive Assessment (MoCA-J). Gait speed was measured to perform gait trials at the patients' usual walking pace, and life-space mobility was evaluated using the Life-Space Assessment (LSA). We investigated the relation between gait speed or life-space mobility and cognitive function by Pearson correlation analysis, whereas multivariable logistic regression analysis was conducted for detecting MCI. Gait speed and LSA scores were positively associated with the MoCA-J score (r = 0.54, p < 0.001 and r = 0.44, p < 0.001, respectively), and both were independently associated with MCI in the multivariable logistic regression analysis (odds ratio 0.007, p < 0.001, and odds ratio 0.98, p = 0.038, respectively). Cognitive impairment can be easily detected by assessment of gait speed and life-space mobility. Interventions to improve gait speed and life-space mobility may lead to the improvement of cognitive function and MCI in patients with CAD.

Association of periodontal disease with atherosclerosis in 70-year-old Japanese older adults.

Periodontal disease and arteriosclerotic disease are greatly affected by aging. In this study, the association of conventional risk factors and periodontal disease with atherosclerosis was longitudinally examined in Japanese older adults. Subjects in this study were 490 community-dwelling septuagenarians (69-71 years) randomly recruited from the Basic Resident Registry of urban or rural areas in Japan. At the baseline examination, all subjects underwent socioeconomic and medical interviews; medical examinations, including examinations for carotid atherosclerosis, hypertension, diabetes mellitus, and dyslipidemia; and conventional dental examinations, including a tooth count and measurement of probing pocket depth (PPD). After 3 years, 182 septuagenarians who had no atherosclerosis at the baseline examination were registered and received the same examination as at the baseline. In the re-examination conducted 3 years after the baseline survey, 131 (72.0%) of the 182 participants who had no atherosclerosis at the baseline examination were diagnosed with carotid atherosclerosis. Adjusting and analyzing the mutual relationships of the conventional risk factors for atherosclerosis by multiple logistic regression analysis for the 171 septuagenarians with a full set of data, the proportion of teeth with PPD ≥ 4 mm was independently related to the prevalence of atherosclerosis (odds ratio: 1.029, P < 0.022). This longitudinal study of Japanese older adults suggests that periodontal disease is associated with the onset/progression of atherosclerosis. Maintaining a healthy periodontal condition may be an important factor in preventing the development and progression of atherosclerosis.

A cross-sectional study of relationships between periodontal disease and general health: The Hitachi Oral Healthcare Survey.

BACKGROUND: This cross-sectional study performed to clarify the relationship between periodontal disease and non-communicable diseases (NCDs), such as obesity, diabetes mellitus, impaired glucose tolerance (IGT), chronic obstructive pulmonary disease (COPD), and atherosclerotic cardiovascular disease (ASCVD) by introducing dental examinations into the annual health examinations conducted by Japanese companies, and to highlights the importance of a medical system that connects dental and medical professionals. METHODS: A total of 1.022 Hitachi Ltd. employees were enrolled in this cross-sectional study. We examined correlations and odds ratios (ORs) between the dental and overall health of employees using stratification and multiple logistic regression analyses based on the periodontal health indicators, general health indicators, and occlusal force. RESULTS: The adjusted OR of PPD for obesity (OR, 1.42; 95% confidence interval [CI], 1.09-1.84; p = 0.009), IGT (OR, 1.48; 95% CI, 1.00-2.20; p = 0.049), and COPD (OR, 1.38; 95% CI, 1.02-1.88; p = 0.038) significantly differed. The adjusted OR of body mass index (OR, 1.28; 95% CI 1.15-1.42; p < 0.001), haemoglobin A1C (HbA1c) (OR, 4.34; 95% CI, 1.89-9.98; p < 0.001), fasting blood glucose (FBG) levels (OR, 1.08; 95% CI 1.04-1.11; p < 0.001), postbronchodilator forced expiratory volume in one second/forced vital capacity ratio (%FEV1) (OR, 0.95; 95% CI 0.91-1.00; p = 0.031) and smoking (OR, 2.32; 95% CI 1.62-3.33; p < 0.001) for severe periodontal disease also significantly differed. Occlusal force was significantly reduced in employees aged 50-59 years compared to those aged 40-49 years. Both PPD, HbA1c, FBG levels were significantly associated with occlusal force among employees with moderate/severe periodontitis. PPD was significantly associated with occlusal force among employees with and moderate COPD, and ASCVD. %FEV1 was significantly associated with occlusal force among employees with IGT. CONCLUSIONS: This cross-sectional study revealed mutual relationships among periodontal disease, NCDs, and occlusal force on Japanese corporate workers. We demonstrated that a comprehensive, regional healthcare system centred on annual integrated dental and physical health examinations in the workplace will benefit employees and positively impact corporate health insurance.

Correlation between leg extensor torque and the degree of sway.

[Purpose] The purpose of this study was to examine the correlation between leg extensor torque and the degree of sway. [Participants and Methods] We recruited 31 male and 22 female healthy adults. Strength Ergo 240 was used to measure leg extensor torque. A body pressure measurement system was used to measure the degree of sway. After the measurement, the correlation between these factors was investigated according to sex. [Results] In the males, a significant negative correlation was observed between leg extensor torque and the degree of sway. [Conclusion] In cases where therapists actively performed muscle strengthening and standing-up exercises to reduce the degree of sway in the males, the possibility that such efforts could increase leg extensor torque was observed.

Correlation between ankle plantar flexor strength and leg extensor torque.

[Purpose] The purpose of this study is to consider the correlation between ankle plantar flexor strength and leg extensor torque in order to investigate whether the leg extension torque can be expected to increase as the triceps surae muscle strength is increased. [Participants and Methods] Healthy adults of 30 males and 22 females were recruited. Hand Held Dynamometer was used to measure ankle plantar flexor strength. Strength Ergo 240 was used to measure leg extensor torque. After measurement, a correlation between these factors was investigated by gender. [Results] For both males and females, a significant positive correlation between the left and right ankle plantar flexor strength and leg extensor torque was observed. [Conclusion] Actively performing muscle strengthening exercises for ankle plantar flexor by physical therapists was found to be meaningful in increasing leg extensor torque.

Identification of genetic risk factors of aggressive periodontitis using genomewide association studies in association with those of chronic periodontitis.

To identify the genetic risk factors for aggressive periodontitis (AgP), it is important to understand the progression and pathogenesis of AgP. The purpose of this review was to summarize the genetic risk factors for AgP identified through a case-control genomewide association study (GWAS) and replication study. The initial studies to identify novel AgP risk factors were potentially biased because they relied on previous studies. To overcome this kind of issue, an unbiased GWAS strategy was introduced to identify genetic risk factors for various diseases. Currently, three genes glycosyltransferase 6 domain containing 1 (GLT6D1), defensin α1 and α3 (DEFA1A3), and sialic acid-binding Ig-like lectin 5 (SIGLEC5) that reach the threshold for genomewide significance have been identified as genetic risk factors for AgP through a case-control GWAS.

Influence of mild cognitive impairment on activities of daily living in patients with cardiovascular disease.

Activities of daily living (ADL) are maintained in patients with mild cognitive impairment (MCI), but, in patients with cardiovascular disease, ADL may have already declined. MCI combined with cardiac disease may accentuate the decline of ADL in these patients. Because the relationship between MCI and ADL in patients with cardiovascular disease is unclear, we examined the associations between MCI and ADL in these patients. We conducted a cross-sectional study of 114 patients with cardiovascular disease but without probable dementia. MCI was estimated with the Japanese version of the Montreal Cognitive Assessment (MoCA-J). We classified patients into the normal cognitive group and MCI group, and compared their clinical characteristics, physical function [Short Physical Performance Battery (SPPB), gait speed, handgrip strength, and knee extensor muscle strength], and ADL [via the Functional Independence Measure (FIM)]. We used logistic regression analysis to evaluate the specific association between MCI and ADL. The incidence of MCI was 36.0%. Significant differences between the two groups were identified for age, body mass index, estimated glomerular filtration rate, albumin, dyslipidemia, educational background, SPPB, gait speed, handgrip strength, and FIM. However, after adjustment for covariates, only FIM was significantly associated with MCI (odds ratio 0.74, 95% confidence interval 0.65-0.84, p < 0.001). ADL was the only independent factor significantly associated with MCI in patients with cardiovascular disease. ADL may be hindered in these patients, even at an early stage of MCI. Therefore, early intervention is necessary to prevent ADL decline from the time of MCI onset or before.

Self-monitoring to increase physical activity in patients with cardiovascular disease: a systematic review and meta-analysis.

BACKGROUND AND AIMS: It is important to encourage physical activity in patients with cardiovascular disease (CVD), and self-monitoring is considered to contribute to increased physical activity. However, the effects of self-monitoring on CVD patients remain to be established. In this study, we examined the influence of self-monitoring on physical activity of patients with CVD via a systematic review and meta-analysis. METHODS: Screening of randomized controlled trials only was undertaken twice on PubMed (date of appraisal: August 29, 2017). The inclusion criteria included outpatients with CVD, interventions for them, daily step counts as physical activity included in the outcome, and self-monitoring included in the intervention. Assessments of the risk of bias and meta-analysis in relation to the mean change of daily step counts were conducted to verify the effects of self-monitoring. RESULTS: From 205 studies retrieved on PubMed, six studies were included, with the oldest study published in 2005. Participants included 693 patients of whom 541 patients completed each study program. Their mean age was 60.8 years, and the ratio of men was 79.6%. From these 6 studies, a meta-analysis was conducted with 269 patients of 4 studies including only RCTs with step counts in the intervention group and the control group, and self-monitoring significantly increased physical activity (95% confidence interval, 1916-3090 steps per day, p < 0.05). The average intervention period was about 5 months. Moreover, four studies involved intervention via the internet, and five studies confirmed the use of self-monitoring combined with other behavior change techniques. CONCLUSION: The results suggest that self-monitoring of physical activity by patients with CVD has a significantly positive effect on their improvement. Moreover, the trend toward self-monitoring combined with setting counseling and activity goals, and increased intervention via the internet, may lead to the future development and spread of self-monitoring for CVD patients.

Activities of daily living at different levels of renal function in elderly hospitalized heart failure patients.

BACKGROUND: Renal function (RF) and activities of daily living (ADL) are risk factors for heart failure (HF) patients. AIMS: We evaluated differences in motor and cognitive ADL in relation to RF in elderly hospitalized HF patients. METHODS: Participants were selected from 414 consecutive hospitalized HF patients based on certain criteria. We investigated patient characteristics including Functional Independence Measure (FIM) and estimated glomerular filtration rate (eGFR). Subjects were divided into three groups by RF level and analyzed with one-way ANOVA and Chi-square tests and two-way ANCOVA and multiple comparison tests. RESULTS: Of the 414 patients, 165 met the inclusion criteria (high RF: 41, moderate RF: 84, low RF: 40). There were significant differences between the three groups in age, eGFR, hemoglobin level, mobility, cognitive function, and length of hospital stay (p < 0.05). Motor FIM showed an interaction between term and group, and cognitive FIM showed a main effect on the group (p < 0.05). In the multiple comparisons, motor FIM of all groups indicated significant recovery, but it was significantly lower after 1 week in the low RF versus moderate/high RF groups (p < 0.05). Cognitive FIM showed no significant recovery in the low RF group; the FIM score after 2 weeks was significantly lower than that in the moderate/high RF groups (p < 0.05). CONCLUSIONS: In elderly hospitalized HF patients, the motor ADL recovery process in the low RF group was delayed compared to the high RF group. Cognitive ADL in hospitalized HF patients is difficult to recover, especially in those with low RF.

FGF-2 promotes initial osseointegration and enhances stability of implants with low primary stability.

OBJECTIVES: The aim of this study was to examine the effect of basic fibroblast growth factor (FGF-2) on osseointegration of dental implants with low primary stability in a beagle dog model. MATERIALS AND METHODS: Customized titanium implants that were designed to have low contact with the existing bone were installed into the edentulous mandible of beagle dogs. To degrade the primary stability of the implants, the diameters of the bone sockets exceeded the implant diameters. FGF-2 (0.3%) plus vehicle (hydroxypropyl cellulose) or vehicle alone was topically applied to the sockets in the FGF-2 and control groups, respectively. In Study 1, the new bone area and length of new bone-to-implant contact (BIC) were evaluated at 4, 8, and 12 weeks after installation using histomorphometry and scanning electron microscopy. In Study 2, the implant stability quotient (ISQ) values were sequentially measured for 16 weeks using an Osstell system. RESULTS: The histomorphometric analysis revealed that the new bone area and length of BIC in the FGF-2 group were significantly larger than those in the control group at 4 weeks. Electron microscopic observation showed intimate contact between the mature lamellar bone and the implant surfaces, osseointegration, in both groups. The ISQ values in the FGF-2 group were significantly increased from 6 to 16 weeks compared with those in the control group. CONCLUSIONS: Taken together, our study demonstrates that FGF-2 promoted new bone formation around the dental implants and subsequent osseointegration, resulting in promotion of stability of implants with low primary stability.

Trophic factors from adipose tissue-derived multi-lineage progenitor cells promote cytodifferentiation of periodontal ligament cells.

Stem and progenitor cells are currently being investigated for their applicability in cell-based therapy for periodontal tissue regeneration. We recently demonstrated that the transplantation of adipose tissue-derived multi-lineage progenitor cells (ADMPCs) enhances periodontal tissue regeneration in beagle dogs. However, the molecular mechanisms by which transplanted ADMPCs induce periodontal tissue regeneration remain to be elucidated. In this study, trophic factors released by ADMPCs were examined for their paracrine effects on human periodontal ligament cell (HPDL) function. ADMPC conditioned medium (ADMPC-CM) up-regulated osteoblastic gene expression, alkaline phosphatase activity and calcified nodule formation in HPDLs, but did not significantly affect their proliferative response. ADMPCs secreted a number of growth factors, including insulin-like growth factor binding protein 6 (IGFBP6), hepatocyte growth factor and vascular endothelial growth factor. Among these, IGFBP6 was most highly expressed. Interestingly, the positive effects of ADMPC-CM on HPDL differentiation were significantly suppressed by transfecting ADMPCs with IGFBP6 siRNA. Our results suggest that ADMPCs transplanted into a defect in periodontal tissue release trophic factors that can stimulate the differentiation of HPDLs to mineralized tissue-forming cells, such as osteoblasts and cementoblasts. IGFBP6 may play crucial roles in ADMPC-induced periodontal regeneration.