Biochemical changes induced by strontium ranelate in differentiating adipocytes

Low bone formation in osteoporosis is associated with a shift from osteoblastic to adipogenic differentiation of mesenchymal stem cells (MSC) inducing a concomitant lipotoxic milieu within the bone marrow. Strontium ranelate (SrRN), a treatment for osteoporosis, has both anti-resorptive and anabolic effects on bone. The anabolic effect of SrRN has been associated with its effect on both osteoblastogenesis and adipogenesis. However, the effect of SrRN on the potentially lipotoxic factors produced by differentiating marrow adipocytes remains poorly understood. To expand the knowledge on the effect of SrRN treatment on the bone microenvironment, we assessed changes in adipogenic factors and adipokine expression in adipocytic differentiation of MSC in vitro. Primary human MSC were induced to differentiate in adipogenic conditions in the presence or absence of SrRN (1–2 mM). We tested the dose-dependent effects of SrRN on adipocyte differentiation including changes in the expression of adipogenic markers and adipokines. We report that adipogenesis was negatively affected in the presence of SrRN with a concomitant dose-dependent decrease in the expression of adipogenic markers and changes in adipokine profile. Taken together, our data suggests that SrRN induces biochemical changes in differentiating adipocytes that could generate a favorable osteogenic effect within the bone marrow milieu.     

小鼠孤雌胚胎干细胞系的建立及生物学特性鉴定

目的:探讨建立合适的小鼠孤雌胚胎干细胞建系方法。方法:采用氯化锶联合细胞松弛素B激活B6D2F1杂交小鼠卵母细胞,所获得的囊胚与桑椹胚分别用于孤雌胚胎干细胞的建系,观察两者的建系成功率。结果:共建立了12株小鼠孤雌胚胎干细胞系,这些细胞SSEA-1抗原阳性,SSEA-4,TRA-1-81,TRA-1-60表面抗原阴性,具有AKP活性,保持正常染色体核型,体内外分化分别形成畸胎瘤和拟胚体。结论:采用囊胚和去透明带的桑葚胚建立孤雌胚胎干细胞系获得成功。该方法为人类纯合子的胚胎干细胞建系提供基础,在自体细胞治疗领域中具有潜在的应用价值。     

Divalent Cation Interactions with Na,K-ATPase Cytoplasmic Cation Sites: Implications for the <Emphasis Type="Italic">para</Emphasis>-Nitrophenyl Phosphatase Reaction Mechanism

The interactions of divalent cations with the adenosine triphosphatase (ATPase) and para-nitrophenyl phosphatase (pNPPase) activity of the purified dog kidney Na pump and the fluorescence of fluorescein isothiocyanate (FITC)-labeled pump were determined. Sr²⁺ and Ba²⁺ did not compete with K⁺ for ATPase (an extracellular K⁺ effect). Sr²⁺ and Ba²⁺ did compete with Na⁺ for ATPase (an intracellular Na⁺ effect) and with K⁺ for pNPPase (an intracellular K⁺ effect). These results suggest that Ba²⁺ or Sr²⁺ can bind to the intracellular transport site, yet neither Ba²⁺ nor Sr²⁺ was able to activate pNPPase activity; we confirmed that Ca²⁺ and Mn²⁺ did activate. As another measure of cation binding, we observed that Ca²⁺ and Mn²⁺, but not Ba²⁺, decreased the fluorescence of the FITC-labeled pump; we confirmed that K⁺ substantially decreased the fluorescence. Interestingly, Ba²⁺ did shift the K⁺ dose-response curve. Ethane diamine inhibited Mn²⁺ stimulation of pNPPase (as well as K⁺ and Mg²⁺ stimulation) but did not shift the 50% inhibitory concentration (IC₅₀) for the Mn²⁺-induced fluorescence change of FITC, though it did shift the IC₅₀ for the K⁺-induced change. These results suggest that the Mn²⁺-induced fluorescence change is not due to Mn²⁺ binding at the transport site. The drawbacks of models in which Mn²⁺ stimulates pNPPase by binding solely to the catalytic site vs. those in which Mn²⁺ stimulates by binding to both the catalytic and transport sites are presented. Our results provide new insights into the pNPPase kinetic mechanism as well as how divalent cations interact with the Na pump.     

Age-related changes in strontium to calcium ratios in rat tissues

The Sr/Ca ratios in plasma, urine, bone, and soft tissues for various ages after weaning in male and female rats were determined to examine the effects of aging on the discrimination between strontium (Sr) and calcium (Ca) under physiological conditions. Age-related changes in the Sr/Ca ratios were similar in all tissues; the Sr/Ca ratios decreased rapidly until about 25-wk-old and then slowly, from that period on, reaching much lower values than in the diet. When the logarithm of the Sr/Ca ratio in each tissue was plotted against the logarithm of age, a linear relationship was observed with statistically significant (p less than 0.05) regression lines. The higher levels of Sr/Ca ratios in all tissues of the younger rats could be explained by the high efficiency of Sr absorption by the small intestine early in life. Parameters for the equations between age and Sr/Ca ratio differed with tissues, suggesting the existence of specific discrimination mechanisms in each tissue.     

Geochemical evidence for the formation of a large miocene “travertine” mound at a sublacustrine spring in a soda lake (Wallerstein castle rock, nördlinger ries, Germany)

Summary “Travertines” (tufa pinnacles) of the Miocene Riescrater basin have been investigated to test whether carbon, oxygen and strontium isotopes can be used for the recognition of fossil subaquatic spring deposits in high-alkalinity settings. The Ries basin “travertines” have so far been interpreted as a product of subaerial to sublacustrine artesian springs discharging calcareous groundwater into a freshwater or slightly saline lake. However, recent studies on microfacies and fabric development propose a formation at Ca²⁺-supplying sublacustrine springs of a soda lake. Geochemical analysis of “travertines” of the castle rock Wallerstein, including “sickle-cell” limestones, thrombolites, non-skeletal stromatolites, and speleothems, now support the latter interpretation. High Sr contents surpassing that of the contemporaneously formed dolomitic algal biocherms of the lake shore point to an aragonitic composition of primary precipitates. the δ¹³C values of diagenetically moderately to weakly altered “travertine” facies types are in the same range of the impact-brecciated Upper Jurassic limestones, thus, are inconsistent with a mixture of soil-derived CO₂ and CO₃ ²⁻ from the Jurassic limestones. In addition, the δ¹⁸O values are too high to support a significant contribution of CO₃ ²⁻ by meteoric waters seeping through marine Jurassic limestones. Instead the δ¹³C and δ¹⁸O values indicate an origin of the CO₃ ²⁻ from a lake water body characterized by evaporation. This is consistent with a sodium-rich lake water as indicated by high sodium contents of aragonitic algal bioherms of the lake shore. The⁸⁷Sr/⁸⁶Sr isotope ratio of the “travertine” mound carbonates are consistent with calculated mixing of spring waters discharging from the crystalline basement and lake water high in dissolved inorganic carbon. This points to an origin of the divalent cations from sublacustrine spring waters. In turn,⁸⁷Sr/⁸⁶Sr isotope ratios of green algal reef carbonates of the lake shore are closer to that of the Upper Jurassic carbonates, due to surface run-off from surrounding limestone uplands.     

Calcium weathering in forested soils and the effect of different tree species

Soil weathering can be an important mechanism to neutralize acidity inforest soils. Tree species may differ in their effect on or response to soilweathering. We used soil mineral data and the natural strontium isotope ratio⁸⁷Sr/⁸⁶Sr as a tracer to identify the effect of treespecies on the Ca weathering rate. The tree species studied were sugar maple(Acer saccharum), hemlock (TsugaCanadensis), American beech (Fagusgrandifolia),red maple (Acer rubrum), white ash (FraxinusAmericana) and red oak (Quercus rubra) growingin a forest in northwestern Connecticut, USA. Three replicated sites dominatedby one of the six tree species were selected. At sugar maple and hemlock sitesthe dominant mineral concentrations were determined at three soil depths. Ateach site soil, soil water and stem wood of the dominant tree species weresampled and analyzed for the ⁸⁷Sr/⁸⁶Sr ratio, total SrandCa content. Atmospheric deposition was collected and analyzed for the sameconstituents. Optical analysis showed that biotite and plagioclaseconcentrations were lower in the soil beneath hemlock than beneath sugar mapleand suggested species effects on mineral weathering in the upper 10cm of the mineral soil. These results could not be confirmed withdata obtained by the Sr isotope study. Within the sensitivity of the Sr isotopemethod, we could not detect tree species effects on Ca weathering andcalculatedCa weathering rates were low at all sites (< 60mgm^–2yr^–1). Wefound a positive correlation between Ca weathering and the total Caconcentration in the surface soil. These results indicate that the absolutedifferences in Ca weathering rate between tree species in these acidic surfacesoils are small and are more controlled by the soil parent material(plagioclasecontent) than by tree species.     

Early Miocene subtropical water temperatures in the southeast Pacific

Cenozoic climate of western South America is strongly controlled by features like Andean uplift and the Humboldt Current. The first strontium isotope age data from central and southern Chile provide a latest Oligocene to late early Miocene age for classic warm-water mollusk faunas reaching as far south as 45°S. Comparison with the biogeography of congeneric living species indicates that sea surface temperatures off central and southern Chile during that time were at least 5 °C higher than today; i.e., minimum annual mean sea surface temperatures for Darwin's Navidad fauna at 34°S are estimated as 20 °C. As expected, the number of tropical taxa decreases towards the south but several are still present as far south as 45°S. The ages scatter relatively broadly between ~ 24 and ~ 16 Ma, partly even within individual localities. Shallow-water and deeper-water faunas are revealed to have similar ages. When considered in light of convincing micropaleontological evidence for late Miocene to early Pliocene depositional ages, the Sr isotope data support a hypothesis that the mollusk fauna is reworked.     

Patterns of root activity and responses of species to nutrients in vegetation of fertile alluvial soil

Temporal pattern of growth, time and depth of root activity, and responses to N, P and K enrichment were measured for the three most abundant species in species-poor vegetation on fertile alluvial soil to examine whether differences in these characteristics could account for their co-existence. The responses of these co-existing species to nutrients were tested in a factorial experiment of N, P and K additions. In the control plots, repeated harvests and injections of Sr at different depths in the soil were used to test differences among species in temporal and spatial pattern of root activity. Root activities were assessed from the Sr concentrations in the aboveground biomass. Differences in temporal pattern of growth and root activity, but not differences in spatial root activity between species, could account for the co-existence of species, since Conium, the most abundant species, was the earliest grown and the deepest-rooted species and it died back when the other two species started to maximize their growth and root activity. In comparison with the second most abundant species Lactuca, Conium had higher N but lower P tissue concentrations. Addition of N favoured Conium and almost eliminated Lactuca, while P and/or K additions increased the abundance of Lactuca and restricted that of Conium. These results provide indications that the differential responses of species to nutrients could be explained by species co-existence also in fertile soils. The changes in vegetation composition after nutrient enrichment could merely be predicted by the species' tissue concentrations of nutrients. The addition of a particular nutrient tended to favor the species with the highest tissue concentration of this nutrient.     

Fish otolith chemistry influenced by exposure to multiple environmental variables

There is an increasing desire for researchers to use the elemental concentrations in fish otoliths to reconstruct environmental histories of fish. These reconstructions may be plausible due to the unique incorporation of elements into discrete layers of otolith material that correspond to daily growth, and because environmental variables of temperature, salinity, and water chemistry can influence otolith chemistry. However, it is essential to establish exactly how temperature, salinity, and the ambient concentration of elements influence otolith chemistry in order to interpret environmental histories of fish. Using a controlled laboratory experiment we tested the relative and interactive effects of temperature, salinity, and ambient concentration of strontium (Sr) and barium (Ba) on the resulting concentration of Sr and Ba in otoliths of black bream Acanthopagrus butcheri (Munro 1949). Salinity and concentration, and temperature and concentration interacted to affect the elemental concentration of Sr:Ca and Ba:Ca in otoliths. Regression analysis revealed that temperature and ambient concentration contributed most to the trend in otolith chemistry for both elements. Importantly, this is the first experiment to combine three environmental variables and assess their effect on otolith chemistry. Based on these results, it should be possible to use changes in the elemental concentration in otoliths to better reconstruct previous environments of temperature, salinity, and ambient water chemistry, which is especially useful when determining occupancy in habitats such as estuaries that display variable environmental characteristics.     

The concentration of manganese,iron, and strontium in hip joint bone obtained from patients undergoing hip replacement surgery

The aim of this study was to determine the concentrations of manganese (Mn), iron (Fe) and strontium (Sr) in the cartilage with adjacent compact bone and spongy bone collected from patients after total hip replacement surgery. In addition, we examined relations between the concentrations of the metals in the bone and selected environmental factors. The concentration of Fe was the highest while Mn concentration was the lowest. The concentrations of Fe in the spongy bone in patients from larger cities were higher than in those living in smaller towns and villages. Significant correlations were found between Fe and Mn concentrations in the cartilage with adjacent compact bone and in the spongy bone, and between Mn and Sr in the spongy bone. In general, Mn, Fe and Sr concentrations in the bones of patients from NW Poland were lower than in other Polish regions and Europe, especially in industrialized countries. In conclusion, it seems that in addition to routine monitoring of the abiotic environment, it is essential to monitor concentrations of heavy metals having a long-term impact in humans.