Normal physiological functions in two animal species with highly different vitamin d status compared to that of humans / Funciones fisiológicas normales en dos especies animales con estatus de vitamina d muy diferentes del actual en seres humanos

Mole rats live in permanent darkness, in networks of underground tunnels (which extend up to 1 km in the subsoil), excavated with their incisors, in warm and semi-arid areas of South Africa. Mole rats have an unusually impoverished vitamin D3 status with undetectable and low plasma concentrations of 25- hydroxyvitamin D3 and 1α,25-dihydroxyvitamin D3, respectively. They express 25-hydroxylase in the liver and 1-hydroxylase and 24-hydroxylase in their kidneys. The presence of specific receptors (VDR) was confirmed in the intestine, kidney, Harderʼs glands and skin. In spite of their poor vitamin D3 status, the apparent fractional intestinal absorption of calcium, magnesium and phosphate was high, always greater than 90%. Oral supplementation with cholecalciferol to mole rats did not improve the efficiency of gastrointestinal absorption of these minerals. Mole ratsdo not display the typical lesion of rickets: hypertrophic and radiolucent growth cartilages. Histological studies reported normal parameters of trabecular and cortical bone quality. Marmosets (monkeys of the New World) are not hypercalcaemic, eventhough they exhibit much higher levels of 25-hydroxyvitamin D3, 1α,25-dihydroxyvitamin D3 and parathyroid hormonethan that of rhesus monkeys and humans. Fed a high vitamin D3 intake (110 IU/day/100 g of body weight), a fraction of the experimental group was found to display osteomalacic changes in their bones: distinct increases in osteoid surface, relative osteoid volume, and active osteoclastic bone resorption. These findings suggest that some marmosets appears to suffer vitamin D-dependent rickets, type II. The maximum binding capacity of the VDR or the dissociation constant of VDR1α,25(OH)2D3 complex of mole rats and New World monkeys are distinctly different of VDR isolated from human cells. Health status of those species appears to be adaptations to the mutations of their VDR. Though rare, as mutations may occur at any time in any patient, the overall message of this review to clinicians may be: recent clinical studies strongly suggests that the normality of physiological functions might be a better indicator of the health status than the serum levels of vitamin D metabolites. (AU)

Las ratas topo viven en la oscuridad permanente, en redes de túneles subterráneos excavadas con sus incisivos (que se extienden hasta 1 km en el subsuelo), en áreas cálidas y semiáridas de Sudáfrica. Las ratas topo tienen un estatus de vitamina D3 inusualmente empobrecido con concentraciones plasmáticas indetectables de 25-hidroxivitamina D3 y bajas de 1α, 25-dihidroxivitamina D3. Poseen 25-hidroxilasa en el hígado y 1-hidroxilasa y 24-hidroxilasa en sus riñones. La presencia de receptores específicos (VDR) ha sido confirmada en el intestino, el riñón, las glándulas de Harder y la piel. A pesar de su pobre estatus de vitamina D3,la absorción fraccional intestinal aparente de calcio, magnesio y fosfato fue alta, siempre superior al 90%. La suplementación oral con colecalciferol a las ratas topo no mejoró la eficacia de la absorción gastrointestinal de estos minerales. No muestran la lesión típica del raquitismo: cartílagos de crecimiento hipertróficos y radiolúcidos. Varios estudios histológicos confirman los hallazgos radiológicos y se informan parámetros normales de la calidad ósea trabecular y cortical. Los titíes (monos del Nuevo Mundo) exhiben calcemias normales con niveles más elevados de 25-hidroxivitamina D3, 1α,25-dihidroxivitamina D3 y hormona paratiroidea que los monos rhesus y los seres humanos. Un tercio de un grupo de titíes alimentados con una alta ingesta de vitamina D3 (110 I/día/100 g de peso corporal) exhibió cambios osteomalácicos en sus huesos: aumento en la superficie osteoide, volumen osteoide y activa reabsorción osteoclástica. Estos hallazgos sugieren que una fracción de la población de titíes padece raquitismo dependiente de vitamina D, tipo II. Debido a mutaciones ocurridas hace millones de años, las máximas capacidades de ligamiento del VDR o los valores de la constante de disociación del complejo VDR-1α,25(OH)2D3 de las ratas topo o monos del Nuevo Mundo son muy diferentes de los verificables en receptores aislados de células humanas actuales. El mensaje de esta revisión a los médicos clínicos podría ser: varios estudios clínicos recientes indican que la normalidad de las funciones fisiológicas de un paciente es un mejor indicador de su salud que los niveles séricos de los metabolitos de la vitamina D. (AU)

Effect of 1, 25-dihydroxy vitamin D3 combined with mechanical strain treatment on proliferation, differentiation, and expression of OPG and RANKL in osteoblastic MC3T3-E1 cells / 医用生物力学

Objective To investigate the effect of 1,25-(OH)2-vitamin D3 (VD3) or mechanical strain alone and their combined treatment on proliferation and differentiation of pre-osteoblast MC3T3-E1 cells in vitro, as well as gene and protein expression of osteoprotegerin (OPG) and receptor activator of nuclear factor-кB ligand (RANKL) in those cells. Methods MC3T3-E1 cells were treated with 10 nmol/L VD3, intermitted mechanical strain or with a combination of these two factors. Cell proliferation was assessed with flow cytometry, and alkaline phosphatase (ALP) activity was measured using a fluorometric detection kit. The mRNA expression of ALP, runt-related transcriptional factor 2 (Runx2), OPG, and RANKL genes was determined by real-time PCR. The proteins expression of Runx2, OPG, and RANKL was determined by Western blotting. ResultsVD3 inhibited the proliferation of MC3T3-E1 cells, but the mechanical strain had no effect on cell proliferation. Mechanical strain, VD3, and the combined treatment enhanced the ALP activity of MC3T3-E1 cells as well as the protein expression of Runx2. The effect of combined treatment was less pronounced than the effect of VD3 or mechanical strain alone. Mechanical strain promoted the gene and protein expression of osteoprotegerin (OPG) and increased the ratio of OPG/RANKL. However, the combination of VD3 and mechanical strain led to a decrease in ratio of OPG/RANKL. Conclusions Mechanical strain might be effective in inducing osteogenic differentiation and increasing bone formation. A joint stimulation with VD3 and strain can decrease proliferation and osteogenic differentiation and increase RANKL expression, which might affect bone remodeling. This study supplies some new data, which might be important in theoretical and clinical research of osteoporosis (OP) and other related bone diseases.

Effects of 1,25-(OH)_2-vitamin D_3 on proliferation, differentiation, and secretion of osteoprotegerin and RANKL in cultured marrow mesenchymal cells of rhesus monkey / 中华内分泌代谢杂志

Objective To study the effects of 1,25-(OH)_2-vitamin D_3[1,25-(OH)_2D_3] on proliferation,differentiation, and secretion of osteoprotegerin and RANK ligand (RANKL)in cultured marrow mesenchymal cells of rhesus monkey (RhBMSCs). Methods Three different concentrations of 1,25-(OH)_2D_3 (10~(-12) ,10~(-10), and 10~(-8)mol/L)were added to the cultured RhBMSCs in vitro. MTT was used to observe cell proliferation and ELISA technique was used to measure the concentration of alkaline phosphatase (ALP), osteocalcin, osteoprotegerin, and RANKL. Mineralization nodus was identified via alizarin red staining. Results Under different concentration of 1,25-(OH)_2D_3, RhBMSCs proliferation were promoted within 7 days but were suppressed beyond 7 days. No significant dose-dependent manner was found. Differentiation of RhBMSCs into osteoblast was promoted by 1,25-(OH)_2D_3. The levels of ALP and osteocalcin in groups with various concentrations of 1,25-(OH)_2D_3 were higher than those of control group [ALP(ng/ml) ,7 d:31.40±1.25,26.50±0.50,28.47± 0.25 vs 13.48±0.26;10 d:33.37±0.68,35.30±1.57,33.27±0.67 vs 17.14±0.55;13 d:35.37±0.12,30.47± 0. 25 , 30. 27±1.25 vs 16.55 ± 1.13 ; osteocalcin (ng/ml), 7 d:4.47±0. 29,4.00 ±0. 60,3.73±0.78 vs 1.63± 0.55;10 d:5.63±0.57,5.17±0.15,4.30±0. 10 vs 2.17±0. 15;13 d:7.03±0.15,5.53±0.25,5.27±0.31 vs 2.23±0. 55 ; all P < 0. 05], but no typical mineralization nodus was found in either group. Secretions of osteoprotegerin and RANKL from RhBMSCs were stimulated by 1,25-(OH)_2D_3 [osteoprotegerin (pg/ml), 7 d: 72.57±0.67,68.00±1.75,64.23±0.87 vs 30. 13±1.72; 10 d:62.03±1.62,51.80±1.30,28.93±0.95 vs 18.13±1.40;13 d:65.13±0.71,62.43±2.11,44.93+1.63 vs 36.70±0.95 ;RANKL(pg/ml) ,7 d:74.33+0.61, 82.37±2.15,85.23±0.45 vs 70.83±1.71 ;10 d:83.30±0.46,86.70±0.56,88.23±0.91 vs 74.20±1.83;13 d: 81.70±1.81,81.07±0.95,84.70±1.41 vs 72.73±0.97 ;all P<0.05]. The secretion of RANKL was increased at first and then decreased, whereas the secretion of osteoprotegerin had the opposite tendency. The secretions of RANKL and osteoprotegerin were both in a dose-dependent manner. Conclusions 1,25-(OH)_2D_3 promotes differentiation of RhBMSCs into osteoblasts,resulting in increased secretions of osteoprotegerin and RANKL

Effects of Insulin-like Growth Factor-I and 1,25-(OH)2 Vitamin D3 Concentration on Intrauterine Growth of Newborns from Mothers with Preeclampsia / 소아과

PURPOSE: This study was undertaken to observe the blood levels of IGF-I and 1,25-(OH)2 Vit. D3 in maternal and neonatal compartments and the effects of IGF-I concentration on intrauterine fetal growth and 1,25-(OH)2 Vit. D3 metabolism in the presence of preeclampsia. METHODS: Thirty-four full-term pregnant women with preeclampsia and their newborns(preeclampsia group) and 10 normotensive full-term pregnant women and their newborns(normotensive group) were observed. IGF-I and 1,25-(OH)2 Vit. D3 concentrations in maternal and umbilical cord blood were analysed. RESULTS: Maternal and umbilical cord blood levels of IGF-I and 1,25-(OH)2 Vit. D3 were significantly lower in the preeclampsia group than in the normotensive group. In the preeclampsia group, maternal and cord blood levels of IGF-I of small-for-gestational age newborns were significantly lower than those of appropriate-for-gestational age newborns. The birth weight and length of newborns correlated with IGF-I concentrations of maternal and umbilical cord blood in small-for-gestational age newborns of preeclampsia group. The correlation between IGF-I and 1,25-(OH)2 Vit. D3 was significant in the umbilical cord blood of preeclampsia group, but only in appropriate-for-gestational age newborns. CONCLUSION: It is suggested that the lower level of IGF-I is the primary factor of intrauterine growth retardation in preeclampsia, and the effect of IGF-I on the metabolism of 1,25-(OH)2 Vit. D3 is different according to the presence of preeclampsia and intrauterine fetal growth retardation.