METHODS: Primary cultures of young, pre-senescent, and senescent fibroblast cells were incubated with γ-tocotrienol for 24 h. The expression levels of ELN, COL1A1, MMP1, CCND1, RB1, and IL6 genes were determined using the quantitative real-time polymerase chain reaction. Cell cycle profiles were determined using a FACSCalibur Flow Cytometer.
RESULTS: The cell cycle was arrested in the G(0)/G(1) phase, and the percentage of cells in S phase decreased with senescence. CCND1, RB1, MMP1, and IL6 were upregulated in senescent fibroblasts. A similar upregulation was not observed in young cells. Incubation with γ-tocotrienol decreased CCND1 and RB1 expression in senescent fibroblasts, decreased cell populations in the G(0)/G(1) phase and increased cell populations in the G(2)/M phase. γ-Tocotrienol treatment also upregulated ELN and COL1A1 and downregulated MMP1 and IL6 expression in young and senescent fibroblasts.
CONCLUSION: γ-Tocotrienol prevented cellular aging in human diploid fibroblasts, which was indicated by the modulation of the cell cycle profile and senescence-associated gene expression.
MATERIALS AND METHODS: Murine MC3T3-E1 preosteoblastic cells were cultured in the different concentrations of AnTT (0.001-1 µg/mL) up to 24 days. Expression of osteoblastic differentiation markers was measured by qPCR (osterix [OSX], collagen 1 alpha 1 [COL1α1], alkaline phosphatase [ALP], and osteocalcin [OCN]) and by fluorometric assay for ALP activity. Detection of collagen and mineralized nodules was done via Direct Red staining and Alizarin Red staining, respectively.
RESULTS: The results showed that osteoblastic differentiation-related genes, such as OSX, COL1α1, ALP, and OCN, were significantly increased in the AnTT-treated groups compared to the vehicle group in a time-dependent manner (P<0.05). Type 1 collagen level was increased from day 3 to day 15 in the AnTT-treated groups, while ALP activity was increased from day 9 to day 21 in the AnTT-treated groups (P<0.05). Enhanced mineralization was observed in the AnTT-treated groups via increasing Alizarin Red staining from day 3 to day 21 (P<0.05).
CONCLUSION: Our results suggest that AnTT enhances the osteogenic activity by promoting the bone formation-related genes and proteins in a temporal and sequential manner.
METHODS: Premenopausal women (n = 136, mean age 41 (±5) years) and postmenopausal women [n = 121, mean age 59 (±4) years] were recruited, and each age group randomised into two groups to take two glasses per day of control = regular milk (500 mg calcium per day) or intervention (Int) = fortified milk (1000 mg calcium for pre-M women and 1200 mg calcium for PM women, 96 mg magnesium, 2.4 mg zinc, 15 µg vitamin D, 4 g FOS-inulin per day). At baseline, week 4 and week 12 serum minerals and bone biochemical markers were measured and bone density was measured at baseline.
RESULTS: Mean 25-hydroxyvitamin D [25(OH) vitamin D3] levels among groups were between 49 and 65 nmol/L at baseline, and over the 12 weeks of supplementation, the fortified milk improved vitamin D status in both Int groups. CTx-1 and PINP reduced significantly in both Pre-M and PM groups over the 12 weeks, with the changes in CTx-1 being significantly different (P
METHODS: One-hundred and twenty-one women (mean age 59 (± 4) years) were randomized into two groups: control (n = 60; regular milk, 428 mg calcium per day) or intervention (n = 61; fortified milk at 1200 mg calcium, 96 mg magnesium, 2.4 mg zinc, 15 μg vitamin D and 4 g FOS-inulin per day). At baseline, weeks 12, 24, 36 and 52, parathyroid hormone (PTH), C-Telopeptide of Type I Collagen (CTx-1), Procollagen I Intact N-Terminal propeptide (PINP) and vitamin D levels were assessed. Bone density (BMD) was measured at baseline and week 52 using a GE Lunar iDXA.
RESULTS: Body mass index, lumbar spine and femoral neck BMD did not differ between groups at baseline. Over 52 weeks, mean plasma 25 (OH) D3 levels increased to 74.8 nmol/L (intervention group) or remained at 63.1 nmol/L (control group) (p
Objectives: The current study aimed at determining the effects of degarelix on bone turnover, bone densitometry, and bone mechanical strength in male rats.
Methods: Eighteen male Sprague-Dawley rats were randomly divided into sham (SHAM), orchidectomized (ORX), and degarelix-induced (DGX) groups. Chemical castration was performed by subcutaneous degarelix injection (2 mg/kg) at the scapular region. The rats were scanned for baseline bone mineral area (BMA), bone mineral content (BMC), and bone mineral density (BMD) using dual-energy x-ray absorptiometry (DXA). Following six weeks of experimental period, BMA, BMC, and BMD were measured again with DXA and blood was collected for testosterone and bone biomarkers (osteocalcin and C-terminal of type I collagen crosslink (CTX-1)) measurements. The rats were euthanized and femora were dissected for bone biomechanical strength analysis.
Results: Bilateral orchidectomy and degarelix administration significantly lowered serum testosterone level, decreased whole body BMC, femoral BMA, femoral BMC, and femoral BMD (P < 0.05) compared with the SHAM group. However, no significant changes were observed in bone biochemical markers and bone mechanical strength in all experimental groups.
Conclusions: In conclusion, degarelix administration had comparable effects on bone as bilateral orchidectomy. Administration of degarelix provides an alternative method of inducing testosterone deficient-osteopenia in male rats without need for removing the testes.