Regulation Of Mineral Homeostasis Research Articles

Chronic kidney disease: a contraindication for using biodegradable magnesium or its alloys as potential orthopedic implants?

Magnesium (Mg) has gained widespread recognition as a potential revolutionary orthopedic biomaterial. However, whether the biodegradation of the Mg-based orthopedic implants would pose a risk to patients with chronic kidney disease (CKD) remains undetermined as the kidney is a key organ regulating mineral homeostasis. A rat CKD model was established by a 5/6 subtotal nephrectomy approach, followed by intramedullary implantation of three types of pins: stainless steel, high pure Mg with high corrosion resistance, and the Mg–Sr–Zn alloy with a fast degradation rate. The long-term biosafety of the biodegradable Mg or its alloys as orthopedic implants were systematically evaluated. During an experimental period of 12 weeks, the implantation did not result in a substantial rise of Mg ion concentration in serum or major organs such as hearts, livers, spleens, lungs, or kidneys. No pathological changes were observed in organs using various histological techniques. No significantly increased iNOS-positive cells or apoptotic cells in these organs were identified. The biodegradable Mg or its alloys as orthopedic implants did not pose an extra health risk to CKD rats at long-term follow-up, suggesting that these biodegradable orthopedic devices might be suitable for most target populations, including patients with CKD.

Bioactives and Biomaterial Construction for Modulating Osteoclast Activities.

Bone tissue constitutes 15-20% of human body weight and plays a crucial role in supporting the body, coordinating movement, regulating mineral homeostasis, and hematopoiesis. The maintenance of bone homeostasis relies on a delicate balance between osteoblasts and osteoclasts. Osteoclasts, as the exclusive "bone resorbers" in the human skeletal system, are of paramount significance yet often receive inadequate attention. When osteoclast activity becomes excessive, it frequently leads to various bone metabolic disorders, subsequently resulting in secondary bone injuries, such as fractures. This not only reduces life quality of patients, but also imposes a significant economic burden on society. In response to the pressing need for biomaterials in the treatment of osteoclast dysregulation, there is a surge of research and investigations aimed at osteoclast regulation. Promising progress is achieved in this domain. This review seeks to provide a comprehensive understanding of how to modulate osteoclast activities. It summarizes bioactive substances that influence osteoclasts and elucidates strategies for constructing related biomaterial systems. It offers practical insights and ideas for the development and application of biomaterials and tissue engineering, with the hope of guiding the clinical treatment of osteoclast-related bone diseases using biomaterials in the future.

Pd(0)‐Catalyzed‐Mediated Synthesis of Vitamin D Compounds

Abstract1α,25‐Dihydroxyvitamin D3 (1,25D3), the hormonally active form of vitamin D3, regulates mineral homeostasis, cell growth, cell differentiation‐proliferation, apoptosis, and immune responses. 1,25D3 activates more than 229 genes associated with several diseases, including arthritis, diabetes and cancer, suggesting its implications in a broader range of biological functions than originally thought. Despite the wide range of biological activities, the clinical applications of 1,25D3 have been limited due to its collateral hypercalcemic effects. This problem has boosted intense synthetic activity in the vitamin D area in the last decades aimed at the development of highly active and non‐calcemic analogs for treatment of hyperproliferative diseases. This review covers the most useful synthetic approaches to 1,25D3 analogs containing the natural vitamin D triene system with emphasis on the Pd(0)‐catalyzed transformations involved in the formation of the vitamin D triene system and A‐ring synthons.

Роль вітаміну D у функціонуванні кісткових клітин

The review summarizes current literature data on the importance of vitamin D in bone cell function. An analytical search was conducted in the PubMed, MEDLINE, Embase, Scopus, and Web of Science databases from January 1, 2018, to June 01, 2023. The vitamin D metabolite 1α,25(OH)2D3 plays an important role in the regulation of mineral homeostasis and bone metabolism. It has catabolic and anabolic actions on osteoblasts, osteocytes and mature osteoclasts. In this review, we describe the direct and indirect effects of 1α,25(OH)2D3 on the function of mesenchymal stromal cells (MSCs), osteoblasts, osteocytes, and osteoclasts. Among the targets of vitamin D action in bone cells are vitamin D receptor (VDR) and cytochrome P450 Family 27 Subfamily B Member 1 (CYP27B1). In osteoblasts and MSCs with CYP27B1 knockout, cell proliferation and differentiation are impaired, and in osteoclasts, the resorption activity and lifespan of these cells are increased. The role of VDR in bone cells was demonstrated in normal and VDR-knockout animal models. The relationship between 1α,25(OH)2D3 – VDR signal transduction by bone cells and calcium balance was analyzed. In osteocytes, as well as in osteoblasts, 1α,25(OH)2D3 regulates the expression of RANKL (receptor activator of nuclear factor kappa-B ligand)), and additionally in osteocytes regulates the expression of FGF-23. The interaction of many other factors in bone cells has been shown to control the biological activity of 1α,25(OH)2D3. Thus, the effect of vitamin D on bone cells is in the phase of active research and requires an in-depth study of the features of its autocrine and paracrine effects. Identification of the molecular links of the mechanism of action of 1α,25(OH)2D3 on bone metabolism will provide a fundamental basis for approaches to the treatment of vitamin D deficiency diseases.

FGF23 and klotho at the intersection of kidney and cardiovascular disease.

Cardiovascular disease is the leading cause of death in patients with chronic kidney disease (CKD). As CKD progresses, CKD-specific risk factors, such as disordered mineral homeostasis, amplify traditional cardiovascular risk factors. Fibroblast growth factor 23 (FGF23) regulates mineral homeostasis by activating complexes of FGF receptors and transmembrane klotho co-receptors. A soluble form of klotho also acts as a 'portable' FGF23 co-receptor in tissues that do not express klotho. In progressive CKD, rising circulating FGF23 levels in combination with decreasing kidney expression of klotho results in klotho-independent effects of FGF23 on the heart that promote left ventricular hypertrophy, heart failure, atrial fibrillation and death. Emerging data suggest that soluble klotho might mitigate some of these effects via several candidate mechanisms. More research is needed to investigate FGF23 excess and klotho deficiency in specific cardiovascular complications of CKD, but the pathophysiological primacy of FGF23 excess versus klotho deficiency might never be precisely resolved, given the entangled feedback loops that they share. Therefore, randomized trials should prioritize clinical practicality over scientific certainty by targeting disordered mineral homeostasis holistically in an effort to improve cardiovascular outcomes in patients with CKD.

Osteoimmunology: A Link between Gastrointestinal Diseases and Skeletal Health in Chickens.

Bone serves as a multifunctional organ in avian species, giving structural integrity to the body, aiding locomotion and flight, regulating mineral homeostasis, and supplementing calcium for eggshell formation. Furthermore, immune cells originate and reside in the bone marrow, sharing a milieu with bone cells, indicating a potential interaction in functions. In avian species, the prevalence of gastrointestinal diseases can alter the growth and the immune response, which costs a great fortune to the poultry industry. Previous studies have shown that coccidiosis and necrotic enteritis can dramatically reduce bone quality as well. However, possible mechanisms on how bone quality is influenced by these disease conditions have not yet been completely understood, other than the reduced feed intake. On the other hand, several mediators of the immune response, such as chemokines and cytokines, play a vital role in the differentiation and activation of osteoclasts responsible for bone resorption and osteoblasts for bone formation. In the case of Eimeria spp./Clostridium perfringens coinfection, these mediators are upregulated. One possible mechanism for accelerated bone loss after gastrointestinal illnesses might be immune-mediated osteoclastogenesis via cytokines-RANKL-mediated pathways. This review article thus focuses on osteoimmunological pathways and the interaction between host immune responses and bone biology in gastrointestinal diseases like coccidiosis and necrotic enteritis affecting skeletal health.

Comparative Transcriptome Analysis Reveals the Effect of miR156a Overexpression on Mineral Nutrient Homeostasis in Nicotiana tabacum.

Mineral nutrition plays an important role in crop growth, yield and quality. MiR156 is a regulatory hub for growth and development. To date, the understanding of miR156-mediated mineral homeostasis is limited. In this study, we overexpressed Nta-miR156a in the tobacco cultivar TN90 and analyzed the effects of miR156 on mineral element homeostasis in tobacco by comparative transcriptome analysis. The results showed that the overexpression of miR156a caused significant morphological changes in transgenic tobacco. Chlorophyll and three anti-resistance markers, proline, total phenolics, and total flavonoids, were altered due to increased miR156 expression levels. Interestingly, the distribution of Cu, Mn, Zn, and Fe in different tissues of transgenic tobacco was disordered compared with that of the wild type. Comparative transcriptome analysis showed that the overexpression of miR156 resulted in 2656 significantly differentially expressed genes. The expression levels of several metal-transport-related genes, such as NtABC, NtZIP, NtHMA, and NtCAX, were significantly increased or decreased in transgenic tobacco. These results suggest that miR156 plays an essential role in regulating mineral homeostasis. Our study provides a new perspective for the further study of mineral nutrient homeostasis in plants.

The impact of vitamin D on cancer: A mini review

In this review, we summarize the most recent advances in vitamin D cancer research to provide molecular clarity, as well as its translational trajectory across the cancer landscape. Vitamin D is well known for its role in regulating mineral homeostasis; however, vitamin D deficiency has also been linked to the development and progression of a number of cancer types. Recent epigenomic, transcriptomic, and proteomic studies have revealed novel vitamin D-mediated biological mechanisms that regulate cancer cell self-renewal, differentiation, proliferation, transformation, and death. Tumor microenvironmental studies have also revealed dynamic relationships between the immune system and vitamin D's anti-neoplastic properties. These findings help to explain the large number of population-based studies that show clinicopathological correlations between circulating vitamin D levels and risk of cancer development and death. The majority of evidence suggests that low circulating vitamin D levels are associated with an increased risk of cancers, whereas supplementation alone or in combination with other chemo/immunotherapeutic drugs may improve clinical outcomes even further. These promising results still necessitate further research and development into novel approaches that target vitamin D signaling and metabolic systems to improve cancer outcomes.

Stoss therapy versus weekly regimen of vitamin D in children with chronic liver disease: a randomized pilot study

BackgroundVitamin D, a hormone involved in the regulation of mineral homeostasis, protects skeletal integrity and modulates cell growth and differentiation. Recently, its potential antifibrotic effects have also been identified. Children with chronic liver disease mostly suffer from vitamin D deficiency. However, little knowledge is known regarding the optimum regimen that can be utilized effectively and safely to correct vitamin D deficiency in these patients and whether it could be effective in reversal or at least halting the progressive process of liver fibrosis. This study is conducted to answer these questions.ResultsTwenty-four children with chronic liver disease (13 boys and 11 girls) were included in the study. Their age ranged from 4.5 to 11.5 years with median age of 8 years. The aetiology of liver disease was heterogenous with autoimmune hepatitis, glycogen storage disease, or chronic hepatitis, and hepatitis C affects the majority. The patients were divided into two matched groups: group A (n:12) that received stoss parenteral intramuscular vitamin D3 (cholecalciferol) therapy (200,000 IU) once followed by 600 IU/day orally for 6 months (this is equivalent to the RDA as maintenance therapy) and group B (n:12) that received 50,000 IU/week oral vitamin D3 (cholecalciferol) therapy in divided daily doses adding on the maintenance dose 600 IU/day for the first 4 weeks followed by only 600 IU/day orally for the rest of the 6 months (5 months). Following vitamin D3 supplementation, in group A (vitamin D stoss therapy group) and group B (vitamin D oral therapy group), there were statistically significant improvement of Ca, alkaline phosphatase, and vitamin D levels, though there was no difference in between both groups. No significant correlation could be found between vitamin D changes and fibroscan changes in either group.ConclusionVitamin D therapy using stoss dose followed by oral therapy or oral vitamin D therapy from the start was equally safe and effective in improving the clinical and laboratory metabolic bone profile abnormalities. Vitamin D effect on liver fibrosis progression or reversion in children is still not understood, and further studies are needed in this field taking in consideration the various causes of liver disease in children.

Genomic mechanisms controlling renal vitamin D metabolism

Vitamin D metabolism centers on regulation in the kidney of CYP27B1 induction by PTH, suppression by FGF23 and 1,25(OH)2D3, and reciprocal CYP24A1 suppression by PTH, and induction by FGF23 and 1,25(OH)2D3. This coordinated genomic regulation through enhancer modules results in the production and dynamic maintenance of circulating endocrine 1,25(OH)2D3 which, together with PTH and FGF23, controls mineral homeostasis. We discovered enhancers near Cyp27b1 in the mouse kidney located within intronic regions of Mettl1 and Mettl21b genes. These kidney-specific enhancers (“M1”, “M21”) control Cyp27b1. Through CRISPR/Cas deletion, we found that PTH activation of Cyp27b1 is lost with deletion of M1, whereas FGF23 suppression is lost with deletion of M21. The combination of both deletions (M1/M21-DIKO) eliminated the suppression by 1,25(OH)2D3. Cyp24a1 activation by 1,25(OH)2D3 is controlled by a promoter proximal pair of VDREs as well as a distal region − 35 to − 37 kb (DS2). We also found that FGF23 activation and PTH suppression of Cyp24a1 was located in a region − 21 to − 37 kb downstream (DS1). More recently, using in vivo ChIP-seq in mouse kidney, we demonstrate that PTH activation rapidly induces increased recruitment of pCREB and its coactivators, CBP and CRTC2, to the M1 and M21 enhancers near the Cyp27b1 gene. At distal enhancers of the Cyp24a1 gene, PTH suppression promotes dismisses CBP with only minor changes in pCREB and CRTC2 occupancy, all of which correlate with a suppression of basal histone acetylation across this locus and reduced transcripts. Surprisingly, we find that 1,25(OH)2D3 suppression increases the occupancy of CRTC2 in the M1 enhancer, a novel observation for CRTC2 and/or 1,25(OH)2D3 action. The suppressive actions of 1,25(OH)2D3 and FGF23 at the Cyp27b1 gene are associated with a reduction in CBP recruitment at these enhancers. Although FGF23-regulated transcription factors remain unknown, we hypothesize that VDR occupancy induced at the M1 and M21 enhancers by 1,25(OH)2D3 likely disrupts or competes with the active conformation of these CREB modules thereby preventing full induction by PTH. Our findings show coactivators such as CRTC2 and CBP contribute to Cyp27b1 and Cyp24a1 transcription and provide molecular insight into the coordinated mechanistic actions of PTH, FGF23, and 1,25(OH)2D3 in the kidney that regulate mineral homeostasis.

An overview of fibroblast growth factor 23 and its role in kidney function

Fibroblast growth factor 23 (FGF23) is a hormone that plays a critical role in regulating mineral homeostasis in the body. Specifically, FGF23 acts on the kidneys to decrease the reabsorption of phosphate from the blood and into the urine. This process helps to reduce serum phosphate levels and maintain balance alongside other hormones such as PTH. The primary responsibility of FGF23 is to regulate the balance of phosphate in the body. It does this by acting on the kidney cells to decrease the reabsorption of phosphate from the blood and into the urine. This process allows the body to excrete excess phosphate to maintain normal serum phosphate levels in the blood. In addition to regulating phosphate levels, FGF23 also plays a role in the metabolism of vitamin D. FGF23 can increase the metabolism of vitamin D to an inactive form, reducing the amount of active vitamin D in the body. This reduction in active vitamin D levels leads to decreased intestinal absorption of dietary calcium and phosphate. Abnormal levels of FGF23 in the body have been associated with several health concerns, particularly in patients with chronic kidney disease. High levels of FGF23 have been linked to the development of bone loss, vascular calcification, and cardiovascular disease. Conversely, low levels of FGF23 have been associated with an increased risk of mortality and cardiovascular disease in patients with kidney disease.

Rapid genomic changes by mineralotropic hormones and kinase SIK inhibition drive coordinated renal Cyp27b1 and Cyp24a1 expression via CREB modules

Vitamin D metabolism centers on kidney regulation of Cyp27b1 by mineralotropic hormones, including induction by parathyroid hormone (PTH), suppression by fibroblast growth factor 23 (FGF23) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), and reciprocal regulations for Cyp24a1. This coordinated genomic regulation results in production of endocrine 1,25(OH)2D3, which, together with PTH and FGF23, controls mineral homeostasis. However, how these events are coordinated is unclear. Here, using invivo chromatin immunoprecipitation sequencing in mouse kidney, we demonstrate that PTH activation rapidly induces increased recruitment of phosphorylated (p-133) CREB (pCREB) and its coactivators, CBP (CREB-binding protein) and CRTC2 (CREB-regulated transcription coactivator 2), to previously defined kidney-specific M1 and M21 enhancers near the Cyp27b1 gene. At distal enhancers of the Cyp24a1 gene, PTH suppression dismisses CBP with only minor changes in pCREB and CRTC2 occupancy, all of which correlate with decreased genomic activity and reduced transcripts. Treatment of mice with salt-inducible kinase inhibitors (YKL-05-099 and SK-124) yields rapid genomic recruitment of CRTC2 to Cyp27b1, limited interaction of CBP, and a transcriptional response for both Cyp27b1 and Cyp24a1 that mirrors the actions of PTH. Surprisingly, we find that 1,25(OH)2D3 suppression increases the occupancy of CRTC2 in the M1 enhancer, a novel observation for CRTC2 and 1,25(OH)2D3 action. Suppressive actions of 1,25(OH)2D3 and FGF23 at the Cyp27b1 gene are associated with reduced CBP recruitment at these CREB-module enhancers that disrupts full PTH induction. Our findings show that CRTC2 contributes to transcription of both Cyp27b1 and Cyp24a1, demonstrate salt-inducible kinase inhibition as a key modulator of vitamin D metabolism, and provide molecular insight into the coordinated mechanistic actions of PTH, FGF23, and 1,25(OH)2D3 in the kidney that regulate mineral homeostasis.

Fibroblast Growth Factor 23 and Osteoporosis: Evidence from Bench to Bedside

Osteoporosis is a chronic debilitating disease caused by imbalanced bone remodeling processes that impair the structural integrity of bone. Over the last ten years, the association between fibroblast growth factor 23 (FGF23) and osteoporosis has been studied in both pre-clinical and clinical investigations. FGF23 is a bone-derived endocrine factor that regulates mineral homeostasis via the fibroblast growth factor receptors (FGFRs)/αKlotho complex. These receptors are expressed in kidney and the parathyroid gland. Preclinical studies have supported the link between the local actions of FGF23 on the bone remodeling processes. In addition, clinical evidence regarding the effects of FGF23 on bone mass and fragility fractures suggest potential diagnostic and prognostic applications of FGF23 in clinical contexts, particularly in elderly and patients with chronic kidney disease. However, inconsistent findings exist and there are areas of uncertainty requiring exploration. This review comprehensively summarizes and discusses preclinical and clinical reports on the roles of FGF23 on osteoporosis, with an emphasis on the local action, as opposed to the systemic action, of FGF23 on the bone. Current gaps in knowledge and future research directions are also suggested to encourage further rigorous research in this important field.

Genistein regulates calcium and phosphate homeostasis without activation of MEK 1/2 signalling pathway in an animal model of the andropause

Soy isoflavone genistein interplays with numerous physiological or pathophysiological processes during ageing. However, its protective role and underlying mechanisms of action in the regulation of calcium (Ca2+) and phosphate (Pi) homeostasis in an animal model of the andropause are yet to be fully clarified. Wistar male rats (16-month-old) were divided into sham-operated, orchidectomized, orchidectomized estradiol-treated (0.625 mg/kg b.m./day) and orchidectomized genistein-treated (30 mg/kg b.m./day) groups. Treatments were administered subcutaneously for 3 weeks, while the controls received vehicle alone. Estradiol treatment increased the expression level of fibroblast growth factor receptor (FGFR) and parathyroid hormone 1 receptor (PTH1R), and activated mitogen – activated protein kinase kinase 1/2 (MEK 1/2) signaling pathway in the kidneys. Genistein application induced a prominent gene and protein expression of Klotho and downregulated the expression of FGFR and PTH1R in the kidney of andropausal rats. Activation of protein kinase B (Akt) signalling pathway was observed, while MEK 1/2 signaling pathway wasn't altered after genistein treatment. The increase of 25 (OH) vitamin D in the serum and decrease in Ca2+ urine content was observed after genistein application. Our findings strongly suggest genistein as a potent biocompound with beneficial effects on the regulation of Ca2+ and Pi homeostasis, especially during aging process when the balance of mineral metabolism is impaired. These novel data provide closer insights into the physiological roles of genistein in the regulation of mineral homeostasis.

Systemic Jak1 activation causes extrarenal calcitriol production and skeletal alterations provoking stunted growth.

Mineral homeostasis is regulated by a complex network involving endocrine actions by calcitriol, parathyroid hormone (PTH), and FGF23 on several organs including kidney, intestine, and bone. Alterations of mineral homeostasis are found in chronic kidney disease and other systemic disorders. The interplay between the immune system and the skeletal system is not fully understood, but cytokines play a major role in modulating calcitriol production and function. One of the main cellular signaling pathways mediating cytokine function is the Janus kinase (JAK)--signal transducer and activator of transcription (STAT) pathway. Here, we used a mouse model (Jak1S645P+/- ) that resembles a constitutive activating mutation of the Jak1/Stat3 signaling pathway in humans, and shows altered mineral metabolism, with higher fibroblast growth factor 23 (FGF23) levels, lower PTH levels, and higher calcitriol levels. The higher calcitriol levels are probably due to extrarenal calcitriol production. Furthermore, systemic Jak1/Stat3 activation led to growth impairment and skeletal alterations. The growth plate in long bones showed decreased chondrocyte proliferation rates and reduced height of terminal chondrocytes. Furthermore, we demonstrate that Jak1 is also involved in bone remodeling early in life. Jak1S645P+/- animals have decreased bone and cortical volume, imbalanced bone remodeling, reduced MAP kinase signaling, and local inflammation. In conclusion, Jak1 plays a major role in bone health probably both, directly and systemically by regulating mineral homeostasis. Understanding the role of this signaling pathway will contribute to a better knowledge in bone growth and in mineral physiology, and to the development of selective Jak inhibitors as osteoprotective agents.

Immunomodulatory Effects of Calcitriol through DNA Methylation Alteration of FOXP3 in the CD4+ T Cells of Mice.

Vitamin D plays a variety of physiological functions, such as regulating mineral homeostasis. More recently, it has emerged as an immunomodulator player, affecting several types of immune cells, such as regulatory T (Treg) cells. It has been reported that vitamin D exerts some mediatory effects through an epigenetic mechanism. In this study, the impacts of calcitriol, the active form of vitamin D, on the methylation of the conserved non-coding sequence 2 (CNS2) region of the forkhead box P3 (Foxp3) gene promoter, were evaluated. Fourteen C57BL/6 mice were recruited in this study and divided into two intervention and control groups. The CD4+ T cells were isolated from mice splenocytes. The expression of Foxp3, IL-10, and transforming growth factor-beta (TGF-β1) genes were relatively quantified by real-time PCR technique, and the DNA methylation percentage of every CpG site in the CNS2 region was measured individually by bisulfite-sequencing PCR. Vitamin D Intervention significantly (p<0.05) could increase the expression of Foxp3, IL-10, and TGF-β1 gene in the CD4+ T cells of mice comparing with the control group. Meanwhile, methylation of the CNS2 region of Foxp3 promoter was significantly decreased in three of ten CpG sites in the vitamin D group compared to the control group. The results of this study showed that vitamin D can engage the methylation process to induce Foxp3 gene expression and probably Treg cytokines profile. Further researches are needed to discover the precise epigenetic mechanisms by which vitamin D modulates the immune system.

Melatonin and nitric oxide enhance cadmium tolerance and phytoremediation efficiency in Catharanthus roseus (L.) G. Don.

In this study, a pot experiment was performed to evaluate the effects of foliar spray with sodium nitroprusside (200 μM SNP) and melatonin (100 μM) singly and in combination on tolerance and accumulation of cadmium (Cd) in Catharanthus roseus (L.) G. Don plants exposed to different levels of cadmium (0, 50, 100, and 200 mg Cd kg-1 soil). The results showed that 50 mg kg-1 Cd had no significant effect on the fresh and dry weight of roots and shoots and content of chlorophyll (Chl) a and b, but the higher levels of Cd (100 and 200 mg kg-1) significantly reduced these attributes and induced an increase in the level of leaf electrolyte leakage and disrupted nutrient homeostasis. The activities of catalase (CAT) and peroxidase (POD) in leaves were increased under lower Cd concentrations (50 and 100 mg kg-1) but decreased under 200 mg kg-1 Cd. However, foliar spray with melatonin and/or SNP increased shoot biomass and the content of Chl a and b, augmented activities of POD and CAT, lowered electrolyte leakage (EL), and improved essential cations homeostasis in leaves. Cadmium content in shoots of C. roseus was less than roots and TF (transfer factor) was < 1. Interestingly, foliar spray with SNP and/or melatonin increased Cd accumulation and bioconcentration factor (BCF) in both roots and shoots and elevated the Cd transport from roots to shoot, as TF values increased in these treatments. The co-application of melatonin and SNP further than their separate usage augmented Cd tolerance through increasing activities of antioxidant enzymes and regulating mineral homeostasis in C. roseus. Furthermore, co-treatment of SNP and melatonin increased Cd phytoremediation efficiency in C. roseus through increasing biomass and elevating uptake and translocation of Cd from root to shoot.

Disrupted expression of genes essential for skeletal muscle fibre integrity and energy metabolism in Vitamin D deficient rats

Vitamin D, a secosteroid that regulates mineral homeostasis via its actions in intestine, bone, kidneys and parathyroid glands, has many other target tissues, including skeletal muscle. In the present study, we used rats to examine if diet-induced vitamin D deficiency or insufficiency altered protein synthesis in muscle via the mTOR pathway, and impaired skeletal muscle quality by changing expression of genes needed for its function. Vitamin D deficiency resulted in reduced levels of phosphorylated mTOR, and suppressed mTOR-dependent phosphorylation of 4E-BP1 and p70-S6K, implying a decrease in activity of the protein synthesis machinery. These changes were coupled with up regulation of genes that are negative regulators of muscle growth (Fbxo32 & Trim63), leading to a net loss of skeletal muscle mass. Vitamin D deficiency or insufficiency also led to a decrease in expression of both myosin and actin-associated proteins (Myh1, Myh2, Myh7, Tnnc1& Tnnt1), which are essential for generation of the mechanical force needed for muscle contraction. We also detected a decrease in expression of glycolytic and oxidative enzyme genes (Hk2, Pfkm, Cs, Pdk4 & βHad) and transcriptional coactivator genes (Ppargc-1α & Ppargc-1β) which indicate a low oxidative capacity of skeletal muscle in the vitamin D deficient state. Furthermore, decreased citrate synthase activity corroborates a decrease in mitochondrial density and aerobic capacity of the muscle. In conclusion, our study demonstrates that chronic vitamin D deficiency or insufficiency reduced the size of skeletal muscle fibres, altered their composition, and decreased their oxidative potential. Most of the changes observed were reversible, either partially or completely, by restoring vitamin D to the diet of the deficient rats.

Vitamin D and Bone.

Vitamin D is a principal factor required for mineral and skeletal homeostasis. Vitamin D deficiency during development causes rickets and in adults can result in osteomalacia and increased risk of fracture. 1,25-Dihydroxyvitamin D3 (1,25(OH)2D3), the hormonally active form of vitamin D, is responsible for the biological actions of vitamin D which are mediated by the vitamin D receptor (VDR). Mutations in the VDR result in early-onset rickets and low calcium and phosphate, indicating the essential role of 1,25(OH)2D3/VDR signaling in the regulation of mineral homeostasis and skeletal health. This chapter summarizes our current understanding of the production of the vitamin D endocrine hormone, 1,25(OH)2D3, and the actions of 1,25(OH)2D3 which result in the maintenance of skeletal homeostasis. The primary role of 1,25(OH)2D3 is to increase calcium absorption from the intestine and thus to increase the availability of calcium for bone mineralization. Specific actions of 1,25(OH)2D3 on the intestine, kidney, and bone needed to maintain calcium homeostasis are summarized, and the impact of vitamin D status on bone health is discussed.

Lowered dietary phosphorus affects intestinal and renal gene expression to maintain mineral homeostasis with immunomodulatory implications in weaned piglets

BackgroundIn monogastric animals, phosphorus (P) homeostasis is maintained by regulating intestinal absorption, bone mobilization, and renal excretion. Since P is a non-renewable resource, a shortage is imminent due to widespread over-usage in the farming and animal husbandry industries. As a consequence, P efficiency should be improved in pig production. We sought to characterize the transcriptional response in re−/absorbing and excreting tissues in pigs to diets varying in calcium: phosphorus ratios. Weaned piglets were assigned to one of three groups fed diets varying in digestible P content for a period of five weeks. Gene expression profiles were analyzed in jejunum, colon, and kidney.ResultsTranscriptome analysis revealed that reduced dietary P intake affects gene expression in jejunum and kidney, but not in colon. The regulation of mineral homeostasis was reflected via altered mRNA abundances of CYP24A1, CYP27A1, TRPM6, SPP1, and VDR in jejunum and kidney. Moreover, lowered abundances of transcripts associated with the classical complement system pathway were observed in the jejunum. In kidney, shifted transcripts were involved in phospholipase C, calcium signaling, and NFAT signaling, which may have immunomodulatory implications.ConclusionsOur results revealed local transcriptional consequences of variable P intake in intestinal and renal tissues. The adaptive responses are the result of organismal efforts to maintain systemic mineral homeostasis while modulating immune features at local tissue sites. Therefore, the deviation from the currently recommended dietary P supply must be carefully considered, as the endogenous mechanisms that respond to low P diets may impact important adaptive immune responses.