Tacrolimus, FK506, promotes bone formation in bone defect mouse model.

OBJECTIVES: Some studies have reported that tacrolimus (FK506), an immunosuppressant, may have positive effects on bone formation. However, the precise effects of FK506 on bone repair or osteoblasts remain inadequately elucidated, and limited research has explored the outcomes of its use in an in vivo mouse model. This study aims to examine the effects of FK506 on bone repair and osteoblast functions using bone defect and BMP-2-induced ectopic ossification mouse models, as well as cultured primary mouse osteoblasts treated with FK506. METHODS: We established mouse models of femur bone defect and BMP-2-induced ectopic ossification to evaluate the effect of FK506 on new bone formation, respectively. Additionally, primary mouse osteoblasts were cultured with FK506 and examined for gene expressions related to osteoblast differentiation. RESULTS: While FK506 promoted the repair of bone defect areas in the femur of the bone defect mouse model, it also led to widespread abnormal bone formation outside the intended area. Additionally, following the implantation of a collagen sponge containing BMP-2 into mouse muscle tissue, FK506 was found to promote ectopic ossification and enhance BMP-2-induced osteoblast differentiation in vitro. Our findings also revealed that FK506 increased the number of immature osteoblasts in the absence of BMP-2 without affecting osteoblast differentiation. Furthermore, direct effects were observed, reducing the ability of osteoblasts to support osteoclastogenesis. CONCLUSIONS: These results indicate that FK506 increases new bone formation during bone repair and influences the proliferation of immature osteoblasts, as well as osteoblast-supported osteoclastogenesis.

Metagenomic Analysis of Bacterial Microflora in Dental and Atherosclerotic Plaques of Patients With Internal Carotid Artery Stenosis.

Background: Internal carotid artery stenosis is primarily attributed to atherosclerosis in the carotid artery bifurcation. Previous studies have detected oral bacteria in atherosclerotic lesions, suggesting an association between oral bacteria and atherosclerosis. In this study, we compared the bacterial flora of the atherosclerotic plaque in the carotid artery and dental plaque of patients with internal carotid artery stenosis using 16S ribosomal RNA (16S rRNA) metagenomic sequencing. Methods: Fifty-four patients who underwent internal carotid endarterectomy for internal carotid artery stenosis at the Showa University Hospital between April 2016 and February 2018 were included. Polymerase chain reaction targeting the 16S rRNA gene detected bacterial DNA in the carotid plaques of 11 cases, of which only 5 could be further analyzed. Thereafter, DNA extracted from the carotid and oral plaques of these 5 cases were analyzed using metagenomic sequencing targeting 16S rRNA. In addition, their general condition and oral conditions were evaluated. The patients were classified into symptomatic and asymptomatic groups based on the presence or absence of symptoms of transient ischemic attack, and their bacterial flora was evaluated. Results: The results demonstrated that the microflora of carotid plaques (n = 5) contained bacterial species from 55 families and 78 genera. In addition, 86.5% of the bacteria detected in the carotid plaques were also detected in oral plaques. Cariogenic and periodontopathic bacteria accounted for 27.7% and 4.7% of the bacteria in the carotid plaques, respectively. Conclusions: These results suggest that oral bacteria are directly or indirectly involved in the pathogenesis of atherosclerosis. More extensive studies of oral commensal bacteria detected in extra-oral lesions are warranted to comprehensively investigate the role of oral bacteria in the pathogenesis of systemic diseases.

Planar catechin increases bone mass by regulating differentiation of osteoclasts in mice.

OBJECTIVES: While catechins have been reported to exhibit potential to benefit osteoporosis patients, the effects of planar catechin (PCat), synthesized during the development of drugs for Alzheimer's disease, have not been clearly elucidated. Here, we examined the effects of PCat on mouse bone metabolism both in vivo and in vitro. METHODS: Six week old female mice were orally administered PCat (30 mg/kg) every other day for four weeks, and their femurs were analyzed using micro-computed tomography imaging. Osteoclasts and osteoblasts were collected from mice and cultured with PCat. Subsequently, osteoclast formation and differentiation and osteoblast differentiation were observed. RESULTS: Mice orally administered PCat displayed significantly increased femur bone mass compared to the control group. Quantitative polymerase chain reaction findings indicated that PCat addition to osteoclast progenitor cultures suppressed osteoclast formation and decreased osteoclast marker expression without affecting the proliferative potential of the osteoclast progenitor cells. Addition of PCat to osteoblast cultures increased osteoblast marker expression. CONCLUSIONS: PCat inhibits osteoclast differentiation and promotes osteoblast differentiation, resulting in increased bone mass in mice. These results suggest that PCat administration is a promising treatment option for conditions associated with bone loss, including osteoporosis.

Effects of lipid metabolism on mouse incisor dentinogenesis.

Tooth formation can be affected by various factors, such as oral disease, drug administration, and systemic illness, as well as internal conditions including dentin formation. Dyslipidemia is an important lifestyle disease, though the relationship of aberrant lipid metabolism with tooth formation has not been clarified. This study was performed to examine the effects of dyslipidemia on tooth formation and tooth development. Dyslipidemia was induced in mice by giving a high-fat diet (HFD) for 12 weeks. Additionally, LDL receptor-deficient (Ldlr-/-) strain mice were used to analyze the effects of dyslipidemia and lipid metabolism in greater detail. In the HFD-fed mice, incisor elongation was decreased and pulp was significantly narrowed, while histological findings revealed disappearance of predentin. In Ldlr-/- mice fed regular chow, incisor elongation showed a decreasing trend and pulp a narrowing trend, while predentin changes were unclear. Serum lipid levels were increased in the HFD-fed wild-type (WT) mice, while Ldlr-/- mice given the HFD showed the greatest increase. These results show important effects of lipid metabolism, especially via the LDL receptor, on tooth homeostasis maintenance. In addition, they suggest a different mechanism for WT and Ldlr-/- mice, though the LDL receptor pathway may not be the only factor involved.

Association between simple evaluation of eating and swallowing function and mortality among patients with advanced dementia in nursing homes: 1-year prospective cohort study.

BACKGROUND: A simple and predictable method of evaluating eating and swallowing has not been yet established; thus, it is difficult to implement advance care planning according to deterioration in this function. This study aimed to clarify the association between a simple evaluation of eating and swallowing function and 1-year mortality in advanced dementia patients in nursing homes in Japan. METHODS: The study included 325 residents with advanced dementia. In a baseline survey, we examined medical history, physical function, and eating and swallowing function. We recorded mortality for 1 year from baseline. Kaplan-Meier survival analysis and Cox proportional regression were performed to investigate the association between the simple evaluation of eating and swallowing function and mortality. RESULTS: Statistical analysis included data from 312 of the 325 residents who had completed the baseline survey (7 individuals with non-oral ingestion and 6 who were alive but did not reside in the nursing home 1 year later were excluded). The participants' mean age was 85.2 years, and 79.5 % of participants were female. At the 1-year follow-up, 70 patients had died. According to Cox proportional regression analysis, age, male gender, history of cerebrovascular disorder, poor results of palpation of masseter muscle tension, and modified water swallowing test were significantly associated with 1-year mortality. CONCLUSION: The results of palpation of masseter muscle tension and modified water swallowing test were associated with 1-year mortality. These routine observations can predict mortality, and may thus provide evidence of the opportunity to implement advance care planning.

Anxiety and depression in patients after surgery for head and neck cancer in Japan.

OBJECTIVE: The present study sought to examine the impact of physical symptoms, facial disfigurement, adequacy of preoperative information, and social support on anxiety and depression in Japanese patients with head and neck cancer (HNC) who had undergone surgery. METHOD: A cross-sectional study with 194 patients was conducted using a self-administered questionnaire. This instruments included the Hospital Anxiety and Depression Scale (HADS), the European Organization for Research and Treatment of Cancer (EORTC) Head and Neck cancer module (QLQ-H&N35), and a Social Support Scale developed by Okabayashi et al. (1997). RESULTS: The majority (56.7%) had surgery two or more years before completing the questionnaire. More than 25% of respondents showed anxiety or depression. Higher levels of perceived social support were associated with lower rates of anxiety and depression (p < 0.01). Sensory problems were associated with anxiety, and reduced sexuality was associated with depression (p < 0.01). Perceived disfigurement and adequacy of preoperative information were not associated with anxiety or depression. SIGNIFICANCE OF RESULTS: Survivors of HNC experience anxiety and depression for an extended period of time. Social support may alleviate the severity of these disorders. More research is needed to confirm the impact of facial disfigurement and that of the preoperative information provided by surgeons on psychological distress in HNC patients.