Senescence of bone marrow mesenchymal stem cells in Wistar male rats receiving normal chow/high-calorie diets with/without vitamin D.

Bone marrow mesenchymal stem cells (BM-MSCs) have a momentous function in the composition of the bone marrow microenvironment because of their many valuable properties and abilities, such as immunomodulation and hematopoiesis. The features and actions of MSCs are influenced by senescence, which may be affected by various factors such as nutritional/micronutrients status, e.g., vitamin D. This study aimed to examine the effects of a high-calorie diet (HCD) with/without vitamin D on BM-MSCs senescence. In the first phase, 48 middle-aged rats were fed a normal chow diet (NCD, n = 24) and an HCD (n = 24) for 26 weeks. Afterward, the rats in each group were randomly divided into three equal subgroups. Immediately, eight-rat from each diet group were sacrificed to assess the HCD effects on the first phase measurements. In the second phase, the remaining 4 groups of rats were fed either NCD or HCD with (6 IU/g) or without vitamin D (standard intake: 1 IU/g); in other words, in this phase, the animals were fed (a) NCD, (b) NCD plus vitamin D, (c) HCD, and (d) HCD plus vitamin D for 4 months. BM-MSCs were isolated and evaluated for P16INK4a, P38 MAPK, and Bmi-1 gene expression, reactive oxygen species (ROS) levels, SA-ß-gal activity, and cell cycle profile at the end of both phases. After 26 weeks (first phase), the ROS level, SA-ß-gal-positive cells, and cells in the G1 phase were significantly higher in HCD-fed rats than in NCD-fed ones (P < 0.05). HCD prescription did not significantly affect cells in the S and G2 phases (p > 0.05). Compared with the NCD-fed animals, P16INK4a and P38 MAPK gene expression were up-regulated in the HCD-fed animals; also, Bmi-1 gene expression was down-regulated (P < 0.05). BM-MSCs from vitamin D-treated rats (second phase) exhibited reduced mRNA levels of P16INK4a and P38 MAPK genes and increased Bmi-1 mRNA levels (all P < 0.05). Vitamin D prescription also declined the percentage of SA-ß-gal-positive cells, ROS levels, and the cells in the G1 phase and increased the cells in the S phase in both NCD and HCD-fed animals (P < 0.05). The reduction of the cells in the G2 phase in rats fed with an NCD plus vitamin D was statistically non-significant (P = 0.128) and significant in HCD plus vitamin D rats (P = 0.002). HCD accelerates BM-MSCs senescence, and vitamin D reduces BM-MSCs senescence biomarkers.

Effects of Vitamin D and Calcium Supplementation on Micro-architectural and Densitometric Changes of Rat Femur in a Microgravity Simulator Model.

BACKGROUND: Revealing data on the role of vitamin D and calcium supplementation in bone health has led some to suggest that vitamin D and calcium treatment could also play a role in protecting bone against microgravity-induced mineral loss. OBJECTIVES: The aim of the present study was to investigate the effects of vitamin D and calcium administration on microscopic and densitometric changes of rat femur in a Microgravity Simulator Model. MATERIALS AND METHODS: After designing a Microgravity Simulator Model, 14 rats were placed in the cages as follows: seven rats as osteoporosis group and seven rats received oral supplement of calcium/vitamin D as the treatment group. Animals were sacrificed after eight weeks and then both femurs were removed. Bone mineral density was measured for one femur from each animal, and morphologic studies were evaluated for the contralateral femur. RESULTS: Bone mineral density of the whole femur in the treatment group was significantly higher than the osteoporosis group (0.168 ± 0.005 vs. 0.153 ± 0.006, P = 0.003). Also, bone mineral content of the whole femur was significantly higher in treatment group (0.415 ± 0.016 vs. 0.372 ± 0.019, P = 0.003). However, resorption eroded surface percentage was higher in the osteoporosis group (18.86 ± 3.71% vs. 9.71 ± 1.61%, P = 0.002). CONCLUSIONS: According to the results of this study, vitamin D and calcium administration might have protective effects against microgravity-induced mineral loss in a Rat Microgravity Simulator Model.