Perceived stress and career planning awareness of Japanese and Taiwanese undergraduate dental hygiene students.

Background/purpose: Dental hygiene students' stress might be rising with increasing undergraduate study content and expansions in dental hygienists' roles and expectations as society changes. This study explored Japanese and Taiwanese dental hygiene students' perceptions of stress and their idea of career planning. Materials and methods: Participants were second- to fourth-year students in the 2020 academic year at Tokyo Medical and Dental University (TMDU; n = 60) and Taipei Medical University (TMU; n = 62). An anonymous questionnaire was distributed, which included questions on demographic information and career planning, as well as the Perceived Stress Scale-10 (PSS-10) and modified Dental Environment Stress questionnaire (DES). Results: The response rates were 100.0% (TMDU) and 96.8% (TMU). The number of participants who chose dental hygiene as the first program choice (P < 0.001) and wished to work as dental hygienists after graduation (P = 0.018) in TMDU was significantly higher than in TMU. There was no significant difference between the two schools' stress levels in both PSS-10 and DES-26. The factors influencing students who wished to work as dental hygienists after graduation were "clinical year or not" (P = 0.007) in TMDU, and the DES factor included items related to lack of confidence in becoming a successful and competent dental hygienist, expectations, and fear of the future (P = 0.033) in TMU. Conclusion: Both schools' students experienced moderate or relatively low levels of stress. TMDU students had higher stress related to academic studies, while TMU students had slightly higher stress related to future anxiety.

Prevalence of Possible Dementia in Patients with Maxillofacial Defects and Difficulty of Inserting Obturator in Maxillectomy Patients: Toward Better Provision of Supportive Care.

As society ages, it is important to understand the prevalence of dementia and the difficulties of inserting prostheses in patients with maxillofacial defects in order to clarify issues in supportive care. We screened 183 patients for dementia using the revised Hasegawa's dementia scale (HDS-R) at the Clinic for Maxillofacial prosthetics, Tokyo Medical and Dental University, and investigated age and sex differences in HDS-R score. We asked 47 of the 183 participants about the difficulty of inserting a maxillofacial obturator prosthesis and collected subjective comments, information about the prosthesis, and data from five assessments. Multiple regression analysis was used to reveal factors associated with insertion difficulty. Overall, 8.7% of the participants were judged to have possible dementia. Men were more likely than women to have possible dementia, and the risk increased with age. Of the 47 participants, 26 reported difficulty inserting their prosthesis, 12 of whom attributed it to their oral defect. Fourteen patients advised following doctor's instructions to practice insertion in order to become accustomed to it. A lower HDS-R score had a significant impact on insertion difficulty. Cognitive function and difficulty inserting maxillary obturator prostheses should be considered in the provision of continuous supportive care to patients with maxillary defects.

Fostering globally competent dental students through virtual team-working, problem-solving and person-centred multi-disciplinary care planning.

Background/purpose: : Development and acquisition of communication, logical thinking, team-building, critical appraisal, critical thinking and person-centred multi-disciplinary care planning must be considered as skill sets and global core competencies for a dental professional. Therefore, an international online study course to foster undergraduate dental students' skill sets in these areas was established and this study aimed to report the perceptions of participants. Materials and methods: An international online course consisting of three levels pertaining to the school year was delivered to dental undergraduates of Japan and Thailand from September to December in 2021. An online questionnaire survey was conducted to obtain feedback from the participants and assess the implementation of the course. Results: In total, 64 responses were obtained from students who participated in all the assigned online sessions and completed the questionnaire (a response rate of 88%). More than 95% of students from each level felt that the programme increased their motivation to study clinical dentistry, and was beneficial for their future and made them appreciate the importance of participating in international exchange. The ratio of favourable respondents was more than 90% with a 95% confidence interval. Conclusion: Fostering globally competent dental students is important and the acquisition of necessary skill sets could be enhanced through international virtual team-working, problem-solving and person-centred multi-disciplinary care planning activities. These are beneficial for undergraduate dental student training so that they graduate with a broader global perspective and an appreciation of the importance of delivering person-centred culturally sensitive dental care.

Three-dimensional evaluation of the dental arch in cleft lip and palate after prosthetic treatment.

PURPOSE: This study aimed to evaluate the stability of the surface of the maxillary teeth and mucosa in cleft lip and palate (CLP) patients with a maxilla defect or tissue deficiency according to the duration of observation and cleft type. METHODS: Pairs of maxillary casts taken from 18 patients at different time points after prosthodontic treatment were investigated in this study. All 36 casts were scanned with an intraoral scanner, and the acquired images were saved in standard tesselation language (STL) files. The two STL files for each patient were then superimposed using three-dimensional (3D) evaluation software, with 3D deviations shown as a color map. Areas with a 3D deviation within ±0.100 mm were defined as stable. The influence of cleft type and duration of observation on the ratio of stable areas to the entire maxillary surface comprising the teeth and mucosa was investigated using multiple regression analysis. Statistical significance was set at p <0.05. RESULTS: Multiple regression analysis showed that the duration of observation was significantly associated with the stable area ratio (B = -23.463, P<.001), whereas cleft type was not (ß = 0.13, P = 0.301). CONCLUSIONS: The maxillary teeth and mucosa of CLP patients changed over time, with stable areas showing a negative correlation with the observation period. However, the stability of the dental arch was not significantly affected by the cleft type. 3D analysis of the casts of CLP patients allowed for measurements and to accurately assess relapse of the maxillary arch after prosthetic treatment.

Effect of Ablative Dose Irradiation on Redistribution and Radioresponse in a Mouse Xenograft Model.

We investigated the effects of ablative dose irradiation on redistribution and radioresponse after the second irradiation in a mouse xenograft model, assuming stereotactic body radiotherapy (SBRT). A human tongue cancer cell line, SAS-Fucci, expressing the fluorescent ubiquitination-based cell cycle indicator (Fucci) that visualizes the cell cycle, was employed in this study. Tumor xenografts formed subcutaneously in nude mice (approximately 6 mm in diameter), with essentially no hypoxic regions, were irradiated at 10 Gy and G2 arrest kinetics were determined using histology sections and a real-time detection method. The second irradiation (10 Gy) was given at intervals of 0 h, 3 h, 1 day, and 4 days after the first irradiation, and tumor regrowth curves were obtained. It was revealed that the ratio of G2-arrested cells showed a much higher peak at 1 day postirradiation compared to 2 Gy, assuming conventional radiotherapy, and gradually decreased thereafter up to 4 days. Tumors irradiated at intervals of 0 h and 1 day demonstrated significantly higher radioresponses than other timings. We conclude that redistribution could contribute to the efficacy of SBRT.

Effects of two-year oral health information provision on changes in gingival crevicular fluid in male day-night shift workers.

Background/purpose: Although dental diseases are related to systemic diseases and daily habits and are known to affect the quality of life, little attention has been paid to the importance of oral hygiene in Japanese working-age adults. We, thus, aimed to assess changes in the periodontal condition of working-age adults after providing regular oral health information at their workplace for two years. Materials and methods: Two years of oral health information were provided to workers at four printing companies. The effectiveness thereof was assessed using gingival crevicular fluid (GCF) test results-lactoferrin (Lf), alpha-1-antitrypsin (AT), and aspartate aminotransferase (AST). Questionnaires on health literacy (HL) and dental terminology were also administered to the workers during annual check-ups. Results: The baseline survey participants included were 234 male workers, of which 104 workers followed the same work schedule/day-night shifts and completed the two-year follow-up survey were examined. Providing continuous oral health information with regular updates did not improve participants' self-administered GCF tests (Lf: P = 0.272, AT: P = 0.723, and AST: P = 0.067), and there were no significant changes in HL, perceived symptoms, and use of interdental cleaning tools. Conclusion: Direct oral health education or examination might be necessary for working-age adults to achieve optimum oral conditions, and one-on-one health information provision might not improve their oral condition. A combination of methods to provide oral health promotion must be considered.

Radiation attenuation properties of materials used to fabricate radiotherapy prostheses in vitro study.

PURPOSE: This study investigates the attenuation of radiation doses by four materials, heat-polymerized, and self-polymerized polymethyl methacrylate (PMMA), putty-type, and injection-type polyvinyl siloxane (PVS) impression material. This in vitro study should aid in the selection of dental materials for radiotherapy prostheses, thereby minimizing the possibility of radiotherapy side effects. METHODS: Specimens of each type were fabricated as a 5 × 5 cm squares with a thickness of 10 mm. Heat-polymerizing PMMA, self-polymerizing PMMA, putty-type PVS impression material, and injection-type PVS impression material were selected. A calibration curve was created to determine the association of radiation doses and grayscale value. A linear accelerator was used to irradiate the specimens. The radiation doses above and below the materials were measured using radiochromic film dosimetry. After film irradiation, the pixel scale of color change was used to determine the radiation dose based on the created calibration curve. The results were exported to find average doses to calculate the percentage of the attenuated dose for a comparison of the four materials. RESULTS: The average attenuated doses of heat-polymerizing PMMA, self-polymerizing PMMA, putty-type PVS, and injection-type PVS were 10.8%, 6.2%, 17.2%, and 14.2% respectively. CONCLUSION: PVS showed higher attenuating radiation exposure compared with PMMA.

GPR110, a receptor for synaptamide, expressed in osteoclasts negatively regulates osteoclastogenesis.

Bone remodeling is precisely regulated mainly by osteoblasts and osteoclasts. Although some G-protein coupled receptors (GPCRs) were reported to play roles in osteoblast function, little is known about the roles in osteoclasts. In this study, we found, for the first time, that the expression of GPR110 increased during osteoclastogenesis. GPR110 belongs to adhesion GPCR and was the functional receptor of N-docosahexaenoyl ethanolamine (also called synaptamide). Synaptamide suppressed osteoclastogenesis induced by receptor activator of nuclear factor-kappa B ligand. Considering that synaptamide is the endogenous metabolite of DHA, we hypothesized that DHA may inhibit osteoclastogenesis by affecting synaptamide/GPR110 signaling. But GPR110 knockout and subsequent rescue experiments revealed a pivotal role of GPR110 in the attenuation of osteoclastogenesis by synaptamide but not by DHA. These results suggest that synaptamide/GPR110 signaling negatively regulates osteoclastogenesis. Our study suggested that ligands of GPR110, such as synaptamide, might be a useful drug for osteoporotic patients.

Critical thinking disposition among Thai dental students.

OBJECTIVES: Critical thinking is recognized as an essential aspect in the training of healthcare professionals, yet it has not been explicitly applied to dental education in Thailand. Therefore, this research study aimed to survey the status of critical thinking disposition among Thai dental students and examine the correlation between critical thinking disposition and academic performance. METHODS: In 2020, 322 students from a Thai dental school were invited to participate in the study and answer an online questionnaire supplying demographic data and Grade Point Average (GPA), and respond to the California Critical Thinking Disposition Inventory (CCTDI). A one-way analysis of variance and Spearman's correlation were used to analyze the data. RESULTS: Overall, 279 of the 322 participants (86.6%) completed the demographic information and CCTDI. Three subscales were found to be in the ambivalent range: truth-seeking (36.8 ± 6.2), systematicity (39.0 ± 5.5), and maturity of judgment (37.1 ± 5.9). Most of the CCTDI subscale scores did not significantly correlate with GPAs, except for systematicity (r = 0.119, p = 0.047) and confidence in reasoning (r = 0.146, p = 0.015). CONCLUSION: This study examined the strengths and weaknesses of the students' critical thinking dispositions. Their GPAs correlated with two critical thinking disposition subscales; however, the results did not guarantee a correlation with academic outcomes. Pedagogical strategies to develop dental students' critical thinking dispositions need to be further assessed.

Gap junctional intercellular communication attenuates osteoclastogenesis induced by activated osteoblasts.

Osteoblasts participate in both bone formation through the synthesis of extracellular matrix and osteoclast differentiation through the expression of osteoclast differentiation factor. Osteoblasts communicate with each other via gap junctions (GJ), which enable small molecules, such as cAMP, to move to adjacent cells. Therefore, we focused on the role of cAMP propagation between osteoblasts via GJ in the osteoclast-supporting activity of osteoblasts. Osteoclast-supporting activity was evaluated by a co-culture system of osteoblasts with bone marrow-derived mononuclear cells. In this system, ablation of Gja1, a gene encoding connexin 43, in osteoblasts promoted osteoclastogenesis induced by prostaglandin E2 (PGE2). A phosphodiesterase 4 inhibitor increased both osteoclastogenesis and the intracellular cAMP concentration ([cAMP]i) in osteoblasts. Individual cell analysis of [cAMP]i in osteoblasts revealed different responses of each osteoblast to PGE2. Moreover, measurement of real-time [cAMP]i demonstrated cAMP movement from cell to cell via GJ. The inhibition of GJ resulted in the upregulation of [cAMP]i in osteoblasts stimulated by PGE2. This study suggested that GJ intercellular communication exerts protective effects against excess osteoclastogenesis via cAMP movement between osteoblasts.

Comparative Blink Analysis in Patients With Established Facial Paralysis Using High-Speed Video Analysis.

ABSTRACT: This study analyzed the blink characteristics of patients with incomplete and complete facial paralysis. The authors measured and compared the palpebral distance, eyelid movement distance, and the eye-closing ratio of blinks in 55 patients with Bell's palsy or Ramsay Hunt syndrome (Bell & Hunt group) and 14 with complete paralysis (Complete Paralysis group). in the Bell & Hunt group, the palpebral distance (7.94 mm) was smaller on the paralyzed side than on the non-paralyzed side (9.61 mm). The eyeclosing ratio and the upper eyelid movement were reduced on the paralyzed side (65.3% versus 93.7%, 4.61 versus 7.97 mm) and in the Complete Paralysis group (25.3% versus 94.7%, 2.10 versus 8.49 mm). In the Bell & Hunt group, movement of the upper eyelid on the paralyzed side was weakened despite palpebral contracture. The Complete Paralysis group exhibited highly reduced movement in both the upper and lower eyelids.

Thawed cryopreserved synovial mesenchymal stem cells show comparable effects to cultured cells in the inhibition of osteoarthritis progression in rats.

Intra-articular injections of mesenchymal stem cells (MSCs) can inhibit the progression of osteoarthritis (OA). Previous reports have used cultured MSCs, but the ability to use thawed cryopreserved MSC stocks would be highly advantageous. Our purpose was to elucidate whether thawed cryopreserved MSCs show comparable inhibitory effects on OA progression in rats to those obtained with cultured MSCs. Cultured rat synovial MSCs or thawed MSCs were compared for in vitro viability and properties. The inhibitory effect of thawed MSCs on OA progression was evaluated by injecting cryopreservation fluid and thawed MSCs in meniscectomized rats. Cartilage degeneration was assessed using gross finding and histological scores. Cultured MSCs were then injected into one knee and thawed MSCs into the contralateral knee of the same individual to compare their effects. Cultured MSCs and MSCs thawed after cryopreservation had comparable in vitro colony formation and chondrogenic potentials. In the rat OA model, the gross finding and histological scores were significantly lower in the thawed MSC group than in the cryopreservation fluid group at 8 weeks. Finally, cartilage degeneration did not differ significantly after injection of cultured and thawed MSCs. In conclusion, thawed MSCs showed comparable inhibitory effects on OA progression to cultured MSCs.

Inhibitory effects of miRNAs in astrocytes on C6 glioma progression via connexin 43.

In many types of tumor cells, cell communication via gap junction is decreased or missing. Therefore, cancer cells acquire unique cytosolic environments that differ from those of normal cells. This study assessed the differences in microRNA (miRNA) expression between cancer and normal cells. MicroRNA microarray analysis revealed five miRNAs that were highly expressed in normal astrocytes compared with that in C6 gliomas. To determine whether these miRNAs could pass through gap junctions, connexin 43 was expressed in C6 glioma cells and co-cultured with normal astrocytes. The co-culture experiment showed the possibility that miR-152-3p and miR-143-3p propagate from normal astrocytes to C6 glioma in connexin 43-dependent and -independent manners, respectively. Moreover, we established C6 glioma cells that expressed miR-152-3p or miR-143-3p. Although the proliferation of these miRNA-expressing C6 glioma cells did not differ from that of empty vectors introduced in C6 glioma cells, cell migration and invasion were significantly decreased in C6 glioma cells expressing miR-152-3p or miR-143-3p. These results suggest the possibility that miRNA produced by normal cells attenuates tumor progression through connexin 43-dependent and -independent mechanisms.

A Validation Study of the Revised Diagnostic Criteria from the International Workshop on Ocular Sarcoidosis at a Single Institute in Japan.

Purpose: To validate the revised criteria of the International Workshop on Ocular Sarcoidosis (IWOS) for the diagnosis of ocular sarcoidosis (OS).Methods: A retrospective chart review study was performed on 323 patients including 51 patients with biopsy-proven sarcoidosis and 272 patients with other uveitis entities. Data on intraocular signs and systemic investigations were collected, and sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and the Youden index were calculated.Results: All intraocular signs and most systemic investigations showed high diagnostic parameters. Sensitivity, specificity, PPV, and NPV of the revised IWOS criteria were 1.000, 0.930, 0.728, and 1.000, respectively. Presumed or probable OS showed lower sensitivity and higher specificity when compared with the best Youden index.Conclusion: The revised IWOS criteria are useful in Japanese patients, but could possibly be improved by modifying the criterion of presumed or probable OS.

Associations of blood pressure levels with clinical events in older patients receiving home medical care.

Some studies reported that excessive blood pressure (BP) control was not appropriate for older people, especially from the viewpoint of quality of life and maintaining sufficient blood flow for tissue perfusion. However, the lower limit of the target BP is still unclear, and there has not yet been a sufficient consensus. Therefore, we investigated the associations of BP levels with clinical events in older patients ~85 years old receiving home medical care. A total of 144 patients were included, who were followed for longer than 3 months in the Osaka Home Care Registry study, a prospective cohort study targeting older patients receiving home medical care in Japan. BP levels were divided into lower and higher groups based on the average systolic blood pressure (SBP). The main outcomes were clinical events, including hospitalizations, falls, and deaths during follow-up. As a result, the hospitalization rate in the SBP below 124 mmHg group was significantly higher than that in the SBP over 124 mmHg group. When comparing the clinical events between the two groups only in participants with hypertension, the same results were obtained. Furthermore, in Cox proportional hazards regression models adjusted by age, sex, and current diseases, the SBP below 124 mmHg group showed a significantly higher rate of required hospitalization (hazard ratio: 7.25, 95% confidence interval: 1.79-29.45). Thus, in older and very frail patients requiring home medical care, an SBP level below 124 mmHg could be a predictive marker of clinical events leading to hospitalization.

Genetic and epigenetic regulation of osteopontin by cyclic adenosine 3' 5'-monophosphate in osteoblasts.

Osteopontin (OPN) is not only a marker of osteoblasts but it is also related to cancer progression and inflammation. The expression of OPN increases in response to inflammatory cytokines, hormones, and mechanical stress. Among them, cyclic-AMP (cAMP) elevating agents stimulate OPN expression in the presence of 1, 25-OH vitamin D3 (VD3). We aimed to clarify the mechanism by which cAMP enhances OPN expression in osteoblastic cells. The OPN promoter (-2335 to +76, OPNp2335) exerted a cell type specific response to forskolin (FK) and VD3. Sequential deletion analysis of OPNp revealed that the OPNp (-833 to +76) contained essential responsive regions to respond to cAMP signaling. In particular, both Vitamin D response element (VDRE, -758 to -743) and osteoblast-specific cis- acting element 2 (OSE2, -695 to -690) were essential for cAMP-mediated OPNp activity. The expression of vitamin D receptor (VDR), but not runt-related transcription factor 2 (Runx2), a nuclear receptor for OSE2, was induced by the treatment of the cells with FK. Although, VD3-induced OPNp activity was slightly enhanced in VDR-overexpressing osteoblasts, it reached the same level as that of osteoblasts induced by both VD3 and FK in the presence of histone deacetylase (HDAC) inhibitor. Moreover, we identified histone acetylation on the OPN promoter region by FK treatment. These results strongly suggest that OPNp activity is controlled by the cAMP signaling via genetic and epigenetic regulations.

[Factors associated with behavioral and psychological symptoms in patients with dementia who received home medical treatment: A cross-sectional study (OHCARE study)].

AIM: The present study investigated the behavioral and psychological symptoms of dementia (BPSD) and pharmacological therapy among elderly people with dementia who received home medical treatment. METHODS: This study was part of the Osaka Home Care Registry study (OHCARE-study). Participants were >65 years old with dementia. Demographic and medical data, BPSD, and the LTCI [long-term care insurance] care-need level were collected. A multiple logistic regression analysis was performed in order to clarify the factors associated with BPSD. RESULTS: Among 110 subjects (82.0±11.3 years old), 64.6% had a diagnosis of dementia, most commonly Alzheimer's dementia. Aside from home medical treatment, 58.1% had a nurse visit, 48.1% received home care, and 40.0% used a day service. The prevalence of BPSD was 53.0%. Those with BPSD most frequently had an LTCI care-need level of 3, and the prevalence of BPSD declined as the level increased after 3. Psychotropic drugs were prescribed in 61.5% of those with BPSD. Antipsychotic drugs were used significantly more frequently in those with nursing care resistance, assault and delusions than in others (all, p <0.005). A multivariate analysis showed that the positive predictor of BPSD was antipsychotic drug use, while negative predictors were an LTCI care-need level and the use of visiting rehabilitation. CONCLUSION: The BPSD in elderly dementia patients receiving home medical treatment were clarified. The LTCI care-need level is an independent predictor of BPSD after adjusting for the activities of daily life. Further longitudinal investigations including the BPSD severity and frequency are needed.

Factors associated with changes of care needs level in disabled older adults receiving home medical care: Prospective observational study by Osaka Home Care Registry (OHCARE).

AIM: To clarify factors associated with changes in care needs level and mortality among disabled older people receiving home medical care over a period of 2.5 years. METHODS: The study included 179 participants, aged ≥65 years, receiving home medical care, who consented to join the Osaka Home Care Registry study. The main outcome was changes in the care needs level of participants eligible for the long-term care insurance system. We investigated the association of changes in care needs level with basic characteristics and care-receiving status. RESULTS: At the 2.5-year follow up, 20.0% of participants showed deteriorated levels, and 41.8% of participants died. In multiple logistic regression, age (odds ratio [OR] 1.10, 95% confidence interval [CI] 1.00-1.21; P = 0.051) and bone joint diseases (OR 0.34, CI 0.09-1.22; P = 0.098) were possible risks associated with deterioration of the care needs level. Male sex (OR 3.28, CI 0.91-11.74; P = 0.068) was a possible risk factor for mortality, and lower serum albumin (OR 0.22, CI 0.07-0.73) was a significant risk factor for mortality. CONCLUSIONS: We clarified the different factors associated with deterioration of the care needs level and mortality among disabled older people. Old age and bone joint diseases might be predictive factors for the further deterioration of independence of physical activity, and a low serum albumin level is considered to be strongly associated with increased mortality. Geriatr Gerontol Int 2019; 19: 1198-1205.

Time course analyses of structural changes in the infrapatellar fat pad and synovial membrane during inflammation-induced persistent pain development in rat knee joint.

BACKGROUND: Osteoarthritis (OA) is a common joint disease in aging societies, which is accompanied by chronic inflammation and degeneration of the joint structure. Inflammation of the infrapatellar fat pad (IFP) and synovial membrane (IFP surface) plays essential roles in persistent pain development in patients with OA. To identify the point during the inflammatory process critical for persistent pain development, we performed a time course histological analysis in a rat arthritis model. METHODS: Wistar rats received single intra-articular injection of monoiodoacetic acid (MIA, 0.2 or 1.0 mg/30 µL) in the right knees or phosphate-buffered saline (PBS, 30 µL) as a control in the left knees. Pain avoidance behaviors (weight-bearing asymmetry and tactile hypersensitivity of the plantar surface of the hind paw) were evaluated on days 0, 1, 3, 5, 7, and 14 after injection. Histological assessments of the knee joint were performed on days 0, 1, 3, 5, and 7 after MIA injection. RESULTS: Weight-bearing asymmetry was observed along with the onset of acute inflammation in both the low- (0.2 mg) and high-dose (1.0 mg) groups. In the low-dose group, weight-bearing asymmetry was completely reversed on day 10, indicating that joint pain seemed to alleviate between days 7 and 10. In contrast, we observed persistent joint pain after day 10 in the high-dose group. Histological assessments of the high-dose group indicated that the initial sign of inflammatory responses was observed in the perivascular region inside the IFP. Inflammatory cell infiltration from the perivascular region to the parenchymal region of the IFP was observed on day 3 and reached the IFP surface (synovial membrane) on day 7. Extensive fibrosis throughout the IFP was observed between days 5 and 7 after MIA injection. CONCLUSION: Our data indicated that acute joint pain occurs along with the onset of acute inflammatory process. Irreversible structural changes in the IFP, such as extensive fibrosis, are observed prior to persistent pain development. Thus, we consider that this process may play important roles in persistent pain development.

Effect of gap junction-mediated intercellular communication on TGF-ß induced epithelial-to-mesenchymal transition.

Epithelial-to-mesenchymal transition (EMT) is the process in which epithelial cells lose cell polarity and cell adhesion with surrounding cells to obtain migratory and invasive abilities. On the other hand, the expression of connexin is decreased or lacked in the many types of tumor cells. This study examined the effect of gap junctional intercellular communication (GJIC) on EMT induced by the transforming growth factor-ß1 (TGF-ß1). To investigate the effect of GJIC on EMT in U2OS cells, smooth muscle 22-α (sm22α) promoter-driven luciferase reporter gene was introduced into Cx43-expressing cells (U2OS-Luc Cx43) and into the control parental cell line (U2OS-Luc). TGF-ß1 induced the expression of EMT markers and the sm22α promoter activity of U2OS-Luc cells. Sm22α promoter activity of U2OS cells was neither dependent on the expression of Cx43 nor on the establishment of GJIC among U2OS cells. Furthermore, we found that the homocellular communication among tumor cells did not affected the tumor cell growth and migration. However, we revealed that tumor cell density was an important factor for tumor cells to acquire metastatic phenotype. Interestingly, the co-culture of U2OS cells with osteoblasts revealed that sm22α promoter activity was inhibited only by the GJIC established between these two cell types. These results suggest that normal osteoblast cells negatively regulate the EMT of tumor cells, at least in part. Thus, Cx43-mediated GJIC may have anti-metastatic activity in tumor cells. Our findings provide a new insight into the role of GJIC in cancer progression and metastasis and identify potential therapeutic targets for the treatment of cancer.