1,25(OH)2D3 and its analogue calcipotriol inhibit the migration of human synovial and mesenchymal stromal cells in a wound healing model - A comparison with glucocorticoids.

Vitamin D analogue calcipotriol is currently used in the local treatment of psoriasis. However, it also has antiproliferative and anti-inflammatory effects in the cells of the joint - suggesting a possible benefit in local treatment of arthritis. In this study, calcipotriol was studied in different in vitro methods to find out its effect on synovial and mesenchymal stromal cells. Primary human cell lines of osteoarthritis or rheumatoid arthritis patients (five mesenchymal stromal cells, MSC, and four synovial stromal cells, SSC) were cultured to study migration and proliferation of the cells in a wound healing model. The media was supplemented with calcipotriol, 1,25(OH)2D3, dexamethasone, betamethasone, methylprednisolone or control solution in 1-100 nM concentrations. To see possible toxic effects of calcipotriol, concentrations up to 10 µM in SSCs and MSCs were studied in apoptosis and necrosis assays in four cell lines. Calcipotriol and 1,25(OH)2D3, as well as the three glucocorticoids, reduced the migration of both SSCs and MSCs. In SSCs, the effect of calcipotriol and 1,25(OH)2D3 was at least as effective as with glucocorticoids, while with MSCs, the glucocorticoids were stronger inhibitors of migration. The antimigratory of calcipotriol and 1,25(OH)2D3 was consistently maintained in 10 µM and 1 µM. Calcipotriol was not toxic to MSCs and SSCs up to concentrations of 10 µM. Calcipotriol, as well as 1,25(OH)2D3, exerts antimigratory and antiproliferative effects on human SSCs and MSCs of the joint. These effects are not caused by apoptosis or necrosis. Both calcipotriol and 1,25(OH)2D3 have similar effects as glucocorticoids without apparent toxicity, suggesting that calcipotriol might be an eligible candidate to the local treatment of arthritis with a broad therapeutic window.

The determinants and longitudinal changes in vitamin D status in middle-age: a Northern Finland Birth Cohort 1966 study.

PURPOSE: Populations living in the Nordic countries are at high risk for vitamin D (VitD) deficiency or insufficiency. To reduce the risk, nationwide interventions based on food fortification and supplementation are being implemented. However, there is limited evidence about the impact of such public health campaigns on target populations. METHODS: We studied an unselected sample of 3650 participants (56.2% females) from the longitudinal Northern Finland Birth Cohort 1966 with repeated measures of serum 25-hydroxyvitamin D [25(OH)D] at ages 31 (1997) and 46 (2012-2013). Timepoints corresponded to the period before and during the food fortification. We examined the effect of VitD intake from the diet and supplementation, body mass index and previous 25(OH)D concentration on 25(OH)D concentration at 46 years using a multivariable linear regression analysis. A 25(OH)D z score adjusted for sex, season, latitude and technical effect was used in the analysis. RESULTS: We observed an increase of 10.6 nmol/L in 25(OH)D, when the baseline 25(OH)D was 54.3 nmol/L. The prevalence of serum 25(OH)D below < 50 nmol/L was halved. The changes were found for both sexes and were more pronounced in winter compared to summer months. Regular VitD supplementation had a significant positive effect on 25(OH)D at the age of 46, as well as had the dietary intake of fortified dairy products and fish, and the previous 25(OH)D concentration. However, the intake of fat-spreads albeit VitD-fortified, did not predict 25(OH)D. CONCLUSION: Our results demonstrated the positive impact of the fortification programme on VitD status in middle-aged population.

Early-onset climacterium is not associated with impaired vitamin D status: a population-based study.

OBJECTIVE: To investigate vitamin D status in women with the onset of the climacteric phase by age 46 as both early menopause and inadequate vitamin D status may increase the risk of adverse health outcomes. METHODS: A cross-sectional study included 2,544, 46-year-old women from a birth cohort. Women were divided into the following two groups according to their menstrual history and follicle-stimulating hormone (FSH) concentration: 1) climacteric (FSH ≥25 IU/L and amenorrhea ≥4 mo, n = 351) and 2) preclimacteric women (FSH <25 IU/L and having regular/irregular menstrual cycles, n = 2,193). Serum 25-hydroxyvitamin D (25(OH)D) concentrations were compared between the groups. A linear regression model was performed to investigate which factors are associated with 25(OH)D status. RESULTS: Mean serum 25(OH)D concentrations were higher in climacteric compared with preclimacteric women (68.1 ±â€Š19.8 nmol/L vs 65.2 ±â€Š19.3 nmol/L, P = 0.01). However, in the linear regression model, climacteric status was not associated with 25(OH)D status (multivariable adjusted mean difference 4.5 nmol/L, 95% confidence interval -1.4 to 10.4, P = 0.137). A total of 76 of the climacteric women were using systemic estrogen hormone therapy (HT). In a subanalysis, including only climacteric women, the use of HT was associated with higher 25(OH)D status (multivariable adjusted mean difference 5.9 nmol/L, 95% confidence interval 1.3-10.5, P = 0.013). CONCLUSIONS: The onset of the climacteric phase by age 46 was not associated with inadequate 25(OH)D concentrations, whereas HT use was associated with higher 25(OH)D status in women with early-onset climacterium.

Crown heights in the permanent teeth of 47,XYY males.

OBJECTIVE: The results in human sex chromosome aneuploidies had shown that the extra Y chromosome increases permanent and deciduous tooth crown sizes in the mesiodistal and labiolingual directions. The hypothesis of the study was that the additional Y chromosome increases the permanent tooth crown growth in a vertical dimension. We also aimed to observe possible sex difference in the permanent tooth crown height. MATERIAL AND METHODS: Data on 15 47,XYY males or males with an extra Y chromosome, nine male relatives (five brothers and four fathers) and 45 male and 48 female population controls had been gathered previously for Professor Lassi Alvesalo's KVANTTI Research Project. The measurements from panoramic radiographs were performed of all the applicable teeth, except the third molars on both sides of the jaws with a sliding digital calliper. RESULTS: All the mean tooth crown heights in the 47,XYY males were larger than in the male population controls and the differences were statistically significant in six teeth in the maxilla and 10 teeth in the mandible. Apart from few teeth, the crown heights in the 47,XYY males were larger than in their male relatives, but the difference between these groups was significant only in one tooth. The differences between sexes were statistically significant in eight teeth in the maxilla. CONCLUSIONS: Based on previous investigations and this work, it is evident that the impact of the extra Y chromosome during tooth crown development is holistic, increasing permanent tooth sizes in three dimensions in a balanced manner.