Table 2 - uploaded by David R Fraser
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In the present study, a method was developed for determining the alimentary tract Ca absorption capacity of ruminant animals by measuring the absorption rate of Sr after the administration of an oral dose of strontium chloride acting as a tracer analogue of Ca. A close correlation between the absorption rates of the two tracers was observed upon si...
Citations
... In primary bovine chondrocytes, Sr promotes proliferation and inhibits differentiation via the TGFβ/SMAD pathway [7]. In sheep and dairy cows, Sr concentration in the blood plasma can serve as an index of ruminal Ca absorption capacity under different states of Ca homeostasis [8,9]. Our previous data uncovered some underlying targets of Sr-mediated Ca 2+ metabolism regulation in bovine ruminal epithelial cells [10]. ...
Background
Strontium (Sr) has similar physicochemical properties as calcium (Ca) and is often used to evaluate the absorption of this mineral. Because the major route of Ca absorption in the bovine occurs in the rumen, it is essential to understand whether Sr impacts the ruminal epithelial cells and to what extent.
Results
In the present study, RNA sequencing and assembled transcriptome assembly were used to identify transcription factors (TFs), screening and bioinformatics analysis in bovine ruminal epithelial cells treated with Sr. A total of 1405 TFs were identified and classified into 64 families based on an alignment of conserved domains. A total of 174 differently expressed TFs (DE-TFs) were increased and 52 DE-TFs were decreased; the biological process-epithelial cell differentiation was inhibited according to the GSEA-GO analysis of TFs; The GO analysis of DE-TFs was enriched in the DNA binding. Protein-protein interaction network (PPI) found 12 hubs, including SMAD4, SMAD2, SMAD3, SP1, GATA2, NR3C1, PPARG, FOXO1, MEF2A, NCOA2, LEF1, and ETS1, which verified genes expression levels by real-time PCR.
Conclusions
In this study, SMAD2, PPARG, LEF1, ETS1, GATA2, MEF2A, and NCOA2 are potential candidates that could be targeted by Sr to mediate cell proliferation and differentiation, as well as lipid metabolism. Hence, these results enhance the comprehension of Sr in the regulation of transcription factors and provide new insight into the study of Sr biological function in ruminant animals.
... In primary bovine chondrocytes, Sr promotes proliferation and inhibits differentiation via the TGFβ/SMAD pathway [7]. In sheep and dairy cows, Sr concentration in the blood plasma can serve as an index of ruminal Ca absorption capacity under different states of Ca homeostasis [8,9]. Our previous data uncovered some underlying targets of Srmediated Ca 2+ metabolism regulation in bovine ruminal epithelial cells [10]. ...
Background: Strontium (Sr) has similar physicochemical properties as calcium (Ca) and is often used to evaluate the absorption of this mineral. Because the major route of Ca absorption in the bovine occurs in the rumen, it is essential to understand whether Sr impacts the ruminal epithelial cells and to what extent.
Results: In the present study, RNA sequencing and assembled transcriptome assembly were used to identify transcription factors (TFs), screening and bioinformatics analysis in bovine ruminal epithelial cells treated with Sr. A total of 1405 TFs were identified and classified into 64 families based on an alignment of conserved domains. A total of 174 differently expressed TFs (DE-TFs) were increased and 52 DE-TFs were decreased; the biological process-epithelial cell differentiation was inhibited according to the GSEA-GO analysis of TFs; The GO analysis of DE-TFs was enriched in the DNA binding. Protein-protein interaction network (PPI) found 12 hubs, including SMAD4, SMAD2, SMAD3, SP1, GATA2, NR3C1, PPARG, FOXO1, MEF2A, NCOA2, LEF1, and ETS1, which verified genes expression levels by real-time PCR.
Conclusions: In this study, SMAD2, PPARG, LEF1, ETS1, GATA2, MEF2A, and NCOA2 are potential candidates that could be targeted by Sr to mediate cell proliferation and differentiation, as well as lipid metabolism. Hence, these results enhance the comprehension of Sr in the regulation of transcription factors and provide new insight into the study of Sr biological function in ruminant animals.
... The rumen and intestinal Ca absorption pathways are the major routes for obtaining Ca in vitro [18]. Given its chemical similarity with Ca, Sr has a similar transport and distribution pathway as Ca in the body; Sr can replace Ca in some physiological processes such as muscle contraction, blood clotting, and secretion of certain hormones [19,20]. Sr has been used as a Ca marker to measure intestinal Ca absorption [21,22]. ...
... Sr has been used as a Ca marker to measure intestinal Ca absorption [21,22]. Sr concentration in the blood plasma after an oral dose of strontium chloride (SrCl 2 ) into the rumen can serve as an index of rumen Ca absorption capacity under different states of Ca homeostasis in sheep and dairy cows [19,23]. However, no study has investigated the effect of Sr on Ca absorption in the bovine rumen. ...
... Hypocalcemia is a metabolic disease caused by the homeostatic imbalance of blood Ca 2+ concentration in cows, which impacts their health, future milk production, and reproductive performance [24,25]. Research suggests that blood plasma Sr level can be used as an index of rumen Ca absorption capacity in sheep and dairy cows [19,23]. A few studies have shown that Sr causes intracellular Ca 2+ concentration oscillations generation in rats and mice [26,27]. ...
Strontium (Sr) belongs to the same group in the periodic table as calcium (Ca). Sr level can serve as an index of rumen Ca absorption capacity; however, the effects of Sr on Ca2+ metabolism are unclear. This study aims to investigate the effect of Sr on Ca2+ metabolism in bovine rumen epithelial cells. The bovine rumen epithelial cells were isolated from the rumen of newborn Holstein male calves (n = 3, 1 day old, 38.0 ± 2.8 kg, fasting). The half maximal inhibitory concentration (IC50) of Sr-treated bovine rumen epithelial cells and cell cycle were used to establish the Sr treatment model. Transcriptomics, proteomics, and network pharmacology were conducted to investigate the core targets of Sr-mediated regulation of Ca2+ metabolism in bovine rumen epithelial cells. The data of transcriptomics and proteomics were analyzed using bioinformatic analysis (Gene Ontology and Kyoto Encyclopedia of genes/protein). Quantitative data were analyzed using one-way ANOVA in GraphPad Prism 8.4.3 and the Shapiro–Wilk test was used for the normality test. Results presented that the IC50 of Sr treatment bovine rumen epithelial cells for 24 h was 43.21 mmol/L, and Sr increased intracellular Ca2+ levels. Multi-omics results demonstrated the differential expression of 770 mRNAs and 2436 proteins after Sr treatment; network pharmacology and reverse transcriptase polymerase chain reaction (RT-PCR) revealed Adenosylhomocysteine hydrolase-like protein 2 (AHCYL2), Semaphoring 3A (SEMA3A), Parathyroid hormone-related protein (PTHLH), Transforming growth factor β2 (TGF-β2), and Cholesterol side-chain cleavage enzyme (CYP11A1) as potential targets for Sr-mediated Ca2+ metabolism regulation. Together these results will improve the current comprehension of the regulatory effect of Sr on Ca2+ metabolism and pave a theoretical basis for Sr application in bovine hypocalcemia.
... Therefore, Sr can be very effective in the prevention and treatment of vertebral fractures impaired by osteoporosis [9], and Sr-doped bone repair material has exhibited a good performance in repairing bone defects caused by bone tumors or injuries [10]. In addition, in a veterinary clinic, Hyde et al. reported that Sr concentration could serve as an index for the Ca absorption capacity of the gastrointestinal tract in ruminants, with a close correlation found between the absorption rates of oral Sr and radioactive Ca in both cows and sheep [11,12]. Hence, we aimed to determine the potential effects of Sr on other tissues in the body. ...
Strontium (Sr) is a trace element found mainly in bone, and it performs a dual action by promoting bone formation and inhibiting bone resorption. Sr has been used to evaluate the gastrointestinal calcium (Ca) absorption capacity of dairy cows due to the similar physicochemical properties of the two elements. However, the possible effects of Sr on dairy cows remain unclear. This study aimed to explore the potential regulatory mechanism of Sr in bovine chondrocytes by performing transcriptomic and proteomic analyses. A total of 111 genes (52 up-regulated and 59 down-regulated) were identified as significantly altered (1.2-fold change and p < 0.05) between control and Sr-treated groups. Moreover, LC-MS-based proteomic analysis detected 286 changed proteins (159 up-regulated and 127 down-regulated) between the control and Sr-treated groups (1.2-fold change and p < 0.05). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotations of a combination analysis of the transcriptomic and proteomic data revealed that the genes were predominantly involved in chondrocyte proliferation and differentiation, fat metabolism, the inflammation process, and immune responses. Overall, our data reveal a potential regulatory mechanism of strontium in bovine chondrocytes, thus providing further insights into the functions and application of Sr in ruminants.
... Thus, because Ca levels in the blood do not reflect intestinal absorption capacity, protocols for using Sr as a surrogate marker have been developed (Milsom et al., 1987;Khan et al., 2013). Studies with cows and sheep have reported a close correlation between the absorption rates of oral Sr and radioactive Ca, indicating that the Sr concentrations in the blood measured orally can serve as an index for Ca absorption capacity of the gastrointestinal tract of dairy cows and sheep (Hyde and Fraser, 2014;Hyde et al., 2019). Although these studies have provided information on the use of Sr, it is unknown to what extent (if any) Sr can affect other tissues in the body. ...
... Some studies have reported that Sr absorption could be used as a surrogate indicator for evaluating Ca absorption in the gastrointestinal tract in dairy cows and sheep (Hyde and Fraser, 2014;Hyde et al., 2019). However, the last few decades have witnessed studies on the effect of Sr in the cartilage and chondrocyte. ...
The present study evaluated the effects of strontium (Sr) on proliferation and differentiation of chondrocytes isolated from dairy cows, and whether Sr exerts its effects via transforming growth factor β (TGFβ) signaling. The chondrocytes were isolated from patellar cartilage from newborn Holstein bull calves (n = 3, 1 day old, 38.0 ± 2.8 kg, fasting) within 15 min after euthanasia, and treated with different concentrations of Sr (0, 0.1, 1, and 10 μg/ml, as SrCl 2 ·6H 2 O). After pretreatment with or without activin receptor-like kinase 5 (ALK5) inhibitor (10 μM SB-505124) for 4 h, chondrocytes were incubated with Sr for another 4 h. Overall effects of Sr were evaluated relative to NaCl as the control. In contrast, the 1 μg/ml Sr-treated group served as the control to determine effects of preincubating with SB-505124. Western blot and qRT-PCR were used for measuring expression of proliferation-, differentiation-, and TGFβ1-responsive factors. Data were analyzed using one-way ANOVA in GraphPad Prism 7.0. Incubation with all doses of Sr increased TGFβ1/ALK5-induced SMAD3 phosphorylation, and at 10 μg/ml it inhibited ALK1-induced SMAD1/5/9 phosphorylation. Expression of mRNA and protein of the proliferation-responsive factors type Ⅱ Collagen α1 (COL2A1) and aggrecan (ACAN) was induced by Sr at 1 μg/ml. In contrast, Sr at 10 μg/ml inhibited the expression of differentiation-responsive factors type Ⅹ Collagen α1 (COL10A1) and secreted phosphoprotein 1 (SPP1), and at 1 μg/ml it had the same effect on alkaline phosphatase (ALPL) mRNA and protein levels. Cells were stained with PI/RNase Staining buffer to assess cell cycle activity using flow-cytometry. Incubation with Sr at 1 and 10 μg/ml induced an increase in the number of cells in the S-phase, leading to an increase in the proliferation index. Incubation with SB-505124 inhibited phosphorylation of SMAD3. Abundance of ACAN and COL2A1 mRNA and protein was lower when cells were pre-incubated with SB-505124. Overall, data indicated that Sr promotes proliferation and inhibits differentiation of primary chondrocytes by directing TGFβ1 signaling towards SMAD3 phosphorylation rather than SMAD1/5/9 phosphorylation. Whether these effects occur in vivo remains to be determined and could impact future application of Sr as an experimental tool in livestock.
... The quadratic effect of dietary calcium concentration on milk fever risk is consistent with a biological model that has increased release of PTH and, consequently, calcitriol (active vitamin D) with a low calcium intake (Goings et al., 1974;Green et al., 1981) reducing risk of hypocalcaemia. At high calcium intakes, it is probable that paracellular uptake of calcium across the gastrointestinal tract (Hoenderop et al., 2005, Hyde andFraser, 2014) An effect of low DCAD diets is to increase calcium excretion in urine (van Mosel et al., 1993, Vagnoni and Oetzel, 1998 and may lower readily available bone calcium, hence bone calcium reserves available for mobilisation after calving. This hypercalciuric effect may be greater with increased duration of exposure to a low DCAD diet pre-calving. ...
... Hyde and Fraser estimated Ca transport in vivo by an administration of stable strontium. In contrast to the abovementioned studies, they observed that rumen Ca transport doubled after treatment of sheep with 1α-OHD 3 (Hyde and Fraser, 2014). However, no satisfying explanation for this inconsistency was found. ...
In comparison to monogastric animals, ruminants show some peculiarities in respect to the regulation of mineral homeostasis, which can be regarded as a concerted interplay between gastrointestinal absorption, renal excretion and bone mobilisation to maintain physiological Ca and phosphate ( P i ) concentrations in serum. Intestinal absorption of Ca or P i is mediated by two general mechanisms: paracellular, passive transport dominates when luminal Ca or P i concentrations are high and transcellular. The contribution of active transport becomes more important when dietary Ca or P i supply is restricted or the demand increased. Both pathways are modulated directly by dietary interventions, influenced by age and regulated by endocrine factors such as 1,25-dihydroxyvitamin D 3 . Similar transport processes are observed in the kidney. After filtration, Ca and P i are resorbed along the nephron. However, as urinary Ca and P i excretion is very low in ruminants, the regulation of these renal pathways differs from that described for monogastric species, too. Furthermore, salivary secretion, as part of endogenous P i recycling, and bone mobilisation participate in the maintenance of Ca and P i homeostasis in ruminants. Saliva contains large amounts of P i for buffering rumen pH and to ensure optimal conditions for the rumen microbiome. The skeleton is a major reservoir of Ca and P i to compensate for discrepancies between demand and uptake. But alterations of the regulation of mineral homeostasis induced by other dietary factors such as a low protein diet were observed in growing ruminants. In addition, metabolic changes, for example, at the onset of lactation have pronounced effects on gastrointestinal mineral transport processes in some ruminant species. As disturbances of mineral homeostasis do not only increase the risk of the animals to develop other diseases, but are also associated with protein and energy metabolism, further research is needed to improve our knowledge of its complex regulation.
... Calcium absorption from the alimentary tract of ruminants occurs not only in the small intestine but also in the rumen (Höller et al., 1988;Beardsworth et al., 1989;Wadhwa and Care, 2000). A technique developed in humans to estimate calcium intestinal absorption capacity (Sips et al., 1994) has been adapted to determine the calcium absorption capacity from the rumen and small intestine of sheep (Hyde and Fraser, 2014). This method measures the concentration of strontium ions in blood after administration of a solution of strontium chloride to either the rumen or the small intestine. ...
... Studies in sheep indicated that infusion of 1α-hydroxyvitamin D 3 (1α-OHD 3 ) for 10 to 14 d, with subsequent elevated blood concentration of 1,25(OH) 2 D, was associated with a significant increase in rumen calcium absorption capacity (Hyde and Fraser, 2014). Although species differences exist in aspects of ruminant calcium homeostasis (Wilkens et al., 2012), it seems possible that an increase in circulating 1,25(OH) 2 D is linked to increased calcium absorption capacity in the rumen and small intestine. ...
Absorption of dietary calcium from the rumen is a quantitatively important process in calcium homeostasis of ruminants. In 3 separate experiments in dairy cows, we applied a technique developed in sheep to measure the rate of strontium (Sr) absorption from the rumen as an indicator of calcium absorption capacity. Absorption from the rumen after an oral dose of SrCl 2 resulted in a maximum plasma concentration of Sr after 1 h, whereas absorption from the small intestine after injection of SrCl 2 into the abomasum through a cannula occurred more slowly. The second experiment demonstrated that the calcium absorption capacity index of the rumen was significantly greater in 21 lactating Friesian cows (230 ± 66, mean ± SEM) than in 6 mature, nonlactating, nonpregnant heifers (101 ± 21, mean ± SEM). In a third experiment, we compared clinically normal cows at the onset of lactation with those that developed parturient paresis. In cows that developed severe hypocalcemia, plasma concentrations of 1,25(OH) 2 D were significantly elevated (144 ± 60 pg/mL vs. 90 ± 54 pg/mL; means ± SEM) and their rumen calcium absorption index was significantly decreased compared with that of clinically normal cows. Evidence suggested that mobilization of calcium from bone as lactation commenced was significantly depressed in paretic cows compared with those that did not show clinical signs of hypocalcemia. Moreover, ruminal stasis suppressed the absorption of calcium from the rumen. We conclude that measurement of Sr concentration in blood plasma after an oral dose of SrCl 2 into the rumen can be used as an index of rumen calcium absorption capacity under different states of calcium homeostasis.
... Santos et al. (2019), using a larger database, found no effect of dietary Mg content and a tendency for dietary Ca content to increase the risk of clinical hypocalcemia. We observed considerable consistency of the earlier meta-analyses evaluating the effects of Ca concentrations in the diet (Lean et al., 2009), with Oetzel (1991, Enevoldsen (1993), and Lean et al. (2006) Ca concentration on clinical hypocalcemia risk is consistent with a biological model that has increased release of PTH and, consequently, 1,25-dihydroxyvitamin D 3 with a low Ca intake (Goings et al., 1974;Green et al., 1981) and probable paracellular uptake of Ca across the gastrointestinal tract (Hoenderop et al., 2005;Hyde and Fraser, 2014) with increased Ca concentrations that may both reduce the risk of clinical hypocalcemia; however, intermediate concentrations of Ca in DM of prepartum diets may increase risk. On balance, a strategy of feeding sufficient Ca seems prudent to allow Ca balance to be maintained when calciuria stimulated by feeding a negative DCAD diet occurs before calving; we found no identifiable benefit of providing amounts of Ca in the diet exceeding this amount. ...
The objectives were to use meta-analytic methods to determine the effects of changes in dietary cation-anion difference (DCAD) prepartum on productive performance and health of dairy cows. The literature was systematically reviewed, searching randomized experiments with transition cows that manipulated the prepartum DCAD or experiments with acidogenic diets in which dietary Ca, P, or Mg was manipulated. Forty-two experiments, including 134 treatment means and 1,803 cows, were included in the meta-analysis. Of those, 5 experiments with 15 treatment means reported responses for 151 nulliparous cows. Data collected included the mineral composition of prepartum diets, parity group prepartum, breed, days on treatment, and means and respective measure of variance for urine pH, dry matter intake (DMI), body weight, body condition, productive performance, concentrations of minerals and metabolites in blood, and incidence of diseases. Mixed effects meta-analyses were conducted weighting by the inverse of standard error of the means squared to account for the precision of each experiment. Models include the effects of DCAD, parity group prepartum, interaction between DCAD and parity group, and other covariates that showed significance in univariable analysis. Final models were selected based on parsimony and model fit. Reducing the prepartum DCAD reduced intake prepartum but improved intake postpartum in both parity groups. Interactions between DCAD and parity group occurred for yields of milk, fat-corrected milk (FCM), fat, and protein because reducing the DCAD improved those responses in parous cows; however, reducing the DCAD either had no effect on yields of milk and protein or reduced the yield of FCM and fat in nulliparous cows. The resulting equations from the statistical models predicted that reducing the DCAD from +200 to −100 mEq/kg would increase blood total Ca on the day of calving from 1.86 to 2.04 ± 0.05 mM, DMI postpartum 1.0 kg/d, and milk yield 1.7 kg/d in parous cows. The increased concentrations of blood total Ca at calving and postpartum explained the marked reduction in risk of milk fever in parous cows with a reduction in DCAD. As the DCAD decreased, the risk of retained placenta and metritis also decreased, resulting in fewer disease events per cow in both nulliparous and parous cows. Dietary concentrations of Ca, P, or Mg prepartum had no effect on DMI or yields of milk and FCM; however, increasing dietary Ca within the study range of 0.16 to 1.98% of dry matter tended to increase the risk of milk fever in parous cows regardless of DCAD fed. Collectively, results support the recommendation of prepartum acidogenic diets to result in a negative DCAD to parous cows with improvements in lactation performance and reduced risk of diseases; however, the range of DCAD fed did not allow for detection of an optimum value for postpartum performance. On the other hand, despite improvements in blood concentrations of Ca and reduction in uterine diseases with a reduction in DCAD fed to nulliparous cows, productive performance was either depressed or unaffected and the limited number of experiments did not provide sufficient evidence for a recommended DCAD for this group of cows.
... Santos et al. (2019), using a larger database, found no effect of dietary Mg content and a tendency for dietary Ca content to increase the risk of clinical hypocalcemia. We observed considerable consistency of the earlier meta-analyses evaluating the effects of Ca concentrations in the diet (Lean et al., 2009), with Oetzel (1991), Enevoldsen (1993), and Lean et al. (2006) Ca concentration on clinical hypocalcemia risk is consistent with a biological model that has increased release of PTH and, consequently, 1,25-dihydroxyvitamin D 3 with a low Ca intake (Goings et al., 1974;Green et al., 1981) and probable paracellular uptake of Ca across the gastrointestinal tract (Hoenderop et al., 2005;Hyde and Fraser, 2014) with increased Ca concentrations that may both reduce the risk of clinical hypocalcemia; however, intermediate concentrations of Ca in DM of prepartum diets may increase risk. On balance, a strategy of feeding sufficient Ca seems prudent to allow Ca balance to be maintained when calciuria stimulated by feeding a negative DCAD diet occurs before calving; we found no identifiable benefit of providing amounts of Ca in the diet exceeding this amount. ...
Prepartum diets influence cow performance for weeks to months postpartum. This observation leads to questions about milk yield and physiological and health responses to diets with negative dietary cation-anion difference (DCAD). Further, responses to increased intake of a diet with lower DCAD (Eq/d) have not been explored using meta-analysis. Our objectives were to explore the effects of prepartum DCAD intake on metabolism and production and health as well as the potential for differences in intake of other macrominer-als to influence responses to differences in DCAD intake using classical meta-analytical methods. Not all treated groups were fed a diet with negative DCAD, and the effect studied is that of reducing the DCAD. We hypothesized that reducing DCAD intake would improve Ca metabolism and postpartum performance. We used a maximum of 58 comparisons from 31 experiments and a total of 1,571 cows. Intakes of DCAD were 2.28 Eq/d and −0.64 Eq/d for the control, higher DCAD and treated, lower DCAD groups, respectively. Diets with lower DCAD reduced urine pH [standardized mean difference (SMD) = 1.90 and weighted mean difference (WMD) −1.23 pH]. Intake of lower DCAD decreased prepartum DMI (SMD = 0.23; WMD = 0.29 kg/d), increased postpartum DMI (SMD = 0.40; WMD = 0.63 kg/d), and increased milk yield (SMD = 0.172). However , we found an interaction with parity; diets with lower DCAD increased milk yield in parous cows (SMD = 0.29; WMD = 1.1 kg/d) but resulted in numerically lower milk yield in nulliparous cows (SMD = −0.20; WMD = 1.28 kg/d) compared with controls. The FCM yield increased with treatment (SMD = 0.12; WMD = 0.56 kg/d); however, yield of treated cows tended to be greater in parous cows but smaller for nulliparous cows compared with controls. Milk fat percentage, milk fat yield, and milk protein percentages were not affected by treatment, although milk protein yield tended to increase in cows fed the lower DCAD diet (SMD = 0.21; WMD = 0.02 kg/d). Treatment increased blood Ca (SMD = 0.53; WMD = 0.13 mM) and P (SMD = 0.40; WMD = 0.13 mM) on the day of calving and Ca postpartum (SMD = 0.36; WMD = 0.06 mM). Treated cows had smaller concentration of blood BHB before calving than controls (SMD = −0.39; WMD = −0.04 mM). Reducing DCAD in cows resulted in decreased risks of clinical hypocalcemia (risk ratio = 0.60) and retained placenta (risk ratio = 0.59), and reduced the odds of metritis (odds ratio = 0.46) and overall disease (OR = 0.61). We observed no effect on risk of abomasal displacement or mastitis and no effect of differences between treated and control cows in Ca intake (g/d) on the outcomes evaluated. A positive role for increased Mg intake between groups for increased milk fat yield and in reducing the risk of retained placenta was identified. Diets with lower DCAD improved performance of parous dairy cows, and our findings suggest a need for more studies on the effects of a lower DCAD on nul-liparous transition cows.
