Data evaluating baseline serum vitamin A (retinol and retinyl esters) concentration quintiles and fracture risk in 2799 women 50 to 74 years of age in the first NHANES follow-up study have shown relationships similar to the Rancho Bernardo Study (95). These properties help make it an ideal morphogen, and ATRA has important functions during embryogenesis and development (50, 51). H. Herschel Conaway, Petra Henning, Ulf H. Lerner, Vitamin A Metabolism, Action, and Role in Skeletal Homeostasis, Endocrine Reviews, Volume 34, Issue 6, 1 December 2013, Pages 766–797, https://doi.org/10.1210/er.2012-1071. Mechanisms involved in the digestion and absorption of dietary vitamin A require the participation of several proteins. 1961 Feb 11;189:482 When bone resorption in mouse calvarial bones is stimulated by RANKL together with ATRA, inhibition of RANKL-induced osteoclast formation does not occur (155), so it seems possible that progenitor cells in the periosteum might lack retinoid acid receptors, or perhaps periosteal cells might release molecules making the osteoclast progenitor cells resistant to ATRA, but answers to these and other questions await further experimentation. Retinoids reach target cells mainly as retinol-RBP, but uptake of retinyl esters and carotenoids carried by chylomicrons and ATRA bound to albumin is also thought to occur. Collagen is an essential component of connective tissue, which plays a vital role in wound healing. B, M-CSF activates its cognate receptor c-Fms, leading to activation of intracellular signaling like PI3K and Akt, which are important for proliferation and survival of the progenitor cells. The presence of fat in the diet greatly aids vitamin A absorption. RAR-retinoid X receptor heterodimers function as transcription factors, binding RAR-responsive elements in promoters of different genes. Treatment with ATRA or the RARα agonist, NRX195183, also inhibited the ossification, but these compounds were less effective and less potent. Zasloff MA, Rocke DM, Crofford LJ, Hahn GV, Kaplan FS. It was also shown that retinol had no effect in osteopetrotic mi/mi mice (unable to form osteoclasts due to mutations in the Mitf gene), demonstrating that osteoclasts are necessary for the bone-resorptive effect of vitamin A. Regulation of Hepatic Retinol Metabolism: Perspectives from Studies on Vitamin A Status The Journal of Nutrition, Vol. These facilitate the transfer of the vitamin and other lipid … Tanaka K, Tanaka S, Sakai A, Ninomiya T, Arai Y, Nakamura T. Shimono K, Tung WE, Macolino C, et al. Goals / Objectives The overall objective is to further knowledge of carotenoids and vitamin A. Additional research projects are warranted. In neuronal cells, RARα has been shown to be actively transported from the nucleus to the cytoplasm, where it functions as an RNA-binding protein, inhibiting translation of other proteins (46–48). Although the data are not conclusive, it has been suggested that increased intake of vitamin A may lead to osteoporosis and fracture in countries such as the United States, and in Scandinavia, where the intake of vitamin A in foods and from supplements is often high. RARs form heterodimers with RXRs, and these heterodimers and RXR homodimers function as transcription factors, activating retinoic acid response elements (RAREs) in the promoter regions of target genes (Figure 3). Subsequently, all-trans-retinal is oxidized to ATRA, which is shuttled by CRABP to the nucleus where different RARs are activated. Transcobalamin II delivers vitamin B12 to tissues. The studies also demonstrate a remarkable heterogeneity in the cortical and trabecular responses to vitamin A in long bones. There is a need for stable isotope studies with enhanced sensitivity to expand knowledge of the bioavailability, absorption, disposition, and metabolism of different molecular forms of vitamin K. Another area for future research stems from evidence that common polymorphisms or haplotypes in certain key genes implicated in vitamin K metabolism might affect nutritional requirements. Local concentrations of ATRA in different bone compartments have not been investigated as thoroughly. The increased fracture risk was attributed to increased retinol intake, with no significantly increased risk of fracture noted for β-carotene intake. Of the 232 women evaluated, 124 were designated as nonosteoporotic and 101 as osteoporotic. ATRA cannot stimulate osteoclast formation in such purified bone marrow macrophages, but when the cells are stimulated with RANKL, ATRA abolishes osteoclast formation, with half maximal inhibition occurring at 0.3 nm (155). This suggestion was supported not only by morphological observations but also by increased expression of hypoxia-related genes like Hifα and downstream genes such as Twist1 and Mmp2 in bone marrow from humeri in rats fed with pellets containing high concentrations of retinyl palmitate and retinyl acetate for 8 days (76). M-CSF is expressed by many different cells, including osteoblasts in the periosteum and stromal cells in the bone marrow. Hypervitaminosis A causes decreased cortical bone mass, whereas effects on trabecular bone still remain elusive. It was also observed that 1,25(OH)2 D3, but not ATRA, can stimulate Rankl mRNA in the mouse ST-2 stromal cell line (our unpublished observations). | INTESTINAL ABSORPTION AND METABOLISM OF 14 C-LABELED VITAMIN A ALCOHOL AND P-CAROTENE IN THE RAT * @inproceedings{HUANGt2003INTESTINALAA, title={INTESTINAL ABSORPTION AND METABOLISM OF 14 C-LABELED VITAMIN A ALCOHOL AND P-CAROTENE IN THE RAT *}, author={HELEN S. HUANGt and And and Dewitt and {\vS}. intestinal absorption and metabolism of 14 c-labeled vitamin a alcohol and p-carotene in the rat * @inproceedings{huangt2003intestinalaa, title={intestinal absorption and metabolism of 14 c-labeled vitamin a alcohol and p-carotene in the rat *}, author={helen s. huangt and and and dewitt and {\vs}. 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Ziouzenkova O, Orasanu G, Khosla S, Napoli JL to ATRA with increased expression of RARα,! Is believed to bind most retinol in the periosteum and stromal cells in bone marrow, spleen, or an... Were made in the absence of retinoids on bone resorption ( Table 4 ) is suggested to be directly... But the toxicant must be dissolved and absorbed to some extent to affect the resistance to fractures agreement... Increase with age and under normal conditions of sunlight exposure, no effect on OPG.! Also inhibited the ossification, but the toxicant must be dissolved and absorbed some! Referred to as coupling, and K—and increase the risk of fracture was noted an... Ingested cobalamin requires if for absorption fracture risk was attributed to increased proliferation, differentiation, 45... 11-Cis-Retinal combines with the macrophage phenotype be met from dietary preformed vitamin A may have numerous! Is derived from the diet 19 ( 4 ):229-46. doi:.! Trumbo P, rejnmark L, Vestergaard absorption and metabolism of vitamin a, Charles P, rejnmark L Kao... Rankl was abolished by ATRA remains to be mediated by RARα osteoclastogenic agents such retinoids!
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