How this observation is linked to regulation of osteoclast formation by ATRA remains to be shown. Results can also be influenced by the vitamin D status. . Kawahara TN, Krueger DC, Engelke JA, Harke JM, Binkley NC. Hydrolysis of chylomicron retinyl esters by lipoprotein lipase is thought to facilitate uptake of retinol in tissues, whereas a transmembrane-spanning receptor encoded by the Stra6 (stimulated by retinoic acid 6) gene is thought to be involved in the uptake of retinol bound to RBP (24) (Figure 3). It goes on continuously in both cortical and trabecular bone. Both high and low retinol intakes were associated with decreased BMD at baseline and at 4-year follow-up. As regards the very interesting observation of decreased numbers of osteoclasts at the endosteal surfaces of cortical bone reported by Lind et al (76), no such observation was reported by Kneissel et al (75). The intestinal absorption and metabolism of vitamin A and beta-carotene in man. Increased bone fragility can be a consequence not only of increased bone resorption, but also of decreased bone formation. No comparison with a compound like 1,25(OH)2 D3 was performed, so it is not possible to judge whether the chicken cultures were free of contaminating cells, such as stromal cells. Henriksen K, Bollerslev J, Everts V, Karsdal MA. Interconversion of Various Forms of Vitamin B6 a. Phosphorylation of Pyridoxine, Pyridoxal and Pyridoxamine b. Effects of vitamin A on bone formation have not been studied in as great a detail and are not as well characterized as effects on bone resorption. This, together with increased mRNA expression of osteoblastic genes like Akp1 and Runx2 in bone marrow close to the endosteal surfaces, suggests locally increased osteoblastic activity. Some studies have suggested that bone fragility might be associated with increased vitamin A intake coupled to decreased vitamin D concentrations. If you are at risk for vitamin A deficiency, speak to your healthcare provider about any medications that you are taking. Intestinal β-carotene bioconversion in humans is determined by a new single-sample, plasma isotope ratio method and compared with traditional and modified area-under-the-curve methods. Corpus ID: 27651673. A cause of hypercalcemia, Hypercalcemia caused by iatrogenic hypervitaminosis A, Case of hypercalcemia secondary to hypervitaminosis A in a 6-year-old boy with autism, Vitamin-A-induced hypercalcemia: response to corticosteroids, Retinoids stimulate periosteal bone resorption by enhancing RANKL, a response inhibited by monomeric glucocorticoid receptor, Dietary reference intakes: vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc, Excessive dietary intake of vitamin A is associated with reduced bone mineral density and increased risk for hip fracture, Serum retinol levels and the risk of fracture, Vitamin A intake and hip fractures among postmenopausal women, Retinol intake and bone mineral density in the elderly: the Rancho Bernardo Study, Serum vitamin A concentration and the risk of hip fracture among women 50 to 74 years old in the United States: a prospective analysis of the NHANES I follow-up study, Childhood cod liver oil consumption and bone mineral density in a population-based cohort of peri- and postmenopausal women: the Nord-Trondelag Health Study, Vitamin A intake and the risk of hip fracture in postmenopausal women: the Iowa Women's Health Study, Nutritional associations with bone loss during the menopausal transition: evidence of a beneficial effect of calcium, alcohol, and fruit and vegetable nutrients and of a detrimental effect of fatty acids, Serum retinyl esters are not elevated in postmenopausal women with and without osteoporosis whose preformed vitamin A intakes are high, Lack of a relation between vitamin and mineral antioxidants and bone mineral density: results from the Women's Health Initiative, Effects of dietary nutrients and food groups on bone loss from the proximal femur in men and women in the 7th and 8th decades of age, Retinol, supplemental vitamin A and bone status, Short-term vitamin A supplementation does not affect bone turnover in men, No effect of vitamin A intake on bone mineral density and fracture risk in perimenopausal women, High serum retinyl esters are not associated with reduced bone mineral density in the Third National Health and Nutrition Examination Survey, 1988–1994, High-dose treatment with vitamin A analogues and risk of fractures, Serum retinoids and β-carotene as predictors of hip and other fractures in elderly women, Marked decrease in plasma antioxidants in aged osteoporotic women: results of a cross-sectional study, Low levels of carotenoids and retinol in involutional osteoporosis, Nutrients, body composition and exercise are related to change in bone mineral density in premenopausal women, Relationships between usual nutrient intake and bone-mineral content of women 35–65 years of age: longitudinal and cross-sectional analysis, Dietary Reference Intakes for Calcium and Vitamin D, Vitamin D: methods of 25 hydroxyvitamin D analysis, targeting at risk populations and selecting thresholds of treatment, A pooled analysis of vitamin D dose requirements for fracture prevention, Vitamin A and retinol intakes and the risk of fractures among participants of the Women's Health Initiative Observational Study, Vitamin D deficiency and high serum levels of vitamin A increase the risk of osteoporosis evaluated by quantitative ultrasound measurements (QUS) in postmenopausal Spanish women, Vitamin D insufficiency together with high serum levels of vitamin A increases the risk for osteoporosis in postmenopausal women, Vitamin D status and nutrition in Europe and Asia, Vitamin D status of Canadians as measured in the 2007 to 2009 Canadian Health Measures Survey, Prevalence and correlates of vitamin D deficiency in US adults, Excess dietary vitamin A in the growing chick: effect of fat source and vitamin D, Effects of hypervitaminosis A and D on skeletal metabolism, The influence of vitamin A on the utilization and amelioration of toxicity of cholecalciferol, 25-hydroxycholecalciferol, and 1,25 dihydroxycholecalciferol in young broiler chickens, Vitamin A antagonizes calcium response to vitamin D in man, Lipid soluble vitamins in gene regulation, Bone remodelling: its local regulation and the emergence of bone fragility. Furthermore, multivitamin or cod liver oil supplementation was associated with a significantly lower risk of any fracture. For osteoclastogenesis to occur, progenitor cells must be activated by macrophage colony-stimulating factor (M-CSF), which is needed for proliferation and survival of osteoclasts, and by receptor activator of nuclear factor-κB (RANK) ligand (RANKL), which is required for osteoclast differentiation. In humans, the most important compounds in this group are vitamin D 3 (also known as cholecalciferol) and vitamin D 2 (ergocalciferol).. Why periosteal osteoclast progenitor cells are not inhibited by ATRA is unclear. "National Research Council. The intracellular tail of RANK expresses several binding sites for TNF-related associated factors (TRAFs), of which TRAF6 seems to be most important (131, 132). Mechanism of the biosynthesis of vitamin A from beta-carotene. In contrast to remodeling, modeling of bone is the process by which new bone is formed without prior resorption, or where resorption occurs without subsequent bone formation. The serum concentration of 25-hydroxyvitamin D [25(OH) D] is the optimal clinical indicator of vitamin D status. Treatment with different bisphosphonates was observed to attenuate the decrease in bone mass, suggesting that the effects of Ro 13–6298 were due to enhanced bone resorption. RANKL activates its receptor RANK, which will recruit TRAF6 and subsequently activate several kinases and downstream transcription factors. These data suggest that RARβ and RARγ are not as important as RARα for inhibition of osteoclastogenesis stimulated by RANKL, but conclusive evidence for this awaits studies where RARβ and RARγ are knocked down by interference silencing or use of cells from mice in which these receptors have been deleted. ATRA does not affect mRNA expression of c-Fms in bone marrow macrophages but decreases mRNA expression of Rank (155). Vitamin A is critical for vision as an essential component of rhodopsin, a protein that absorbs light in the retinal receptors, and because it supports the normal differentiation and functioning of the conjunctival membranes and cornea . FcRγ/DAP12 signaling causes activation of phospholipase Cγ (PLCγ), a rise of intracellular calcium, and subsequent activation of the phosphatase calcineurin. The site of major vitamin A absorption was the proximal small intestine and high intake of vitamin A reduced slightly the percentage over-all absorption. The hormone form calcitriol (vitamin D) acts with two other hormones. Vitamin A is required for important physiological processes, including embryogenesis, vision, cell proliferation and differentiation, immune regulation, and glucose and lipid metabolism. Similarly, ATRA (2.5 μm) has been noted to stimulate alkaline phosphatase activity, Osteocalcin mRNA, and mineralization in the preadipocyte cell line 3T3-L1 (170, 171). The authors concluded that ATRA stimulates formation of osteoclasts lacking bone-resorbing activity. Iguratimod inhibits osteoclastogenesis by modulating the RANKL and TNF-α signaling pathways. Solon FS, Solon MS, Mehansho H, et al. Summary of the Effects by Retinoids on Bone Resorption and Osteoclast Formation in Vivo. Furthermore, no statistically significant relationship between vitamin A supplement use or serum retinol to radial bone mass or fracture was reported in a study of 246 postmenopausal women 48 to 80 years of age in a rural Iowa community in the United States (102). Similarly, the synthetic acyclic retinoid, geranylgeranoic acid, also inhibited osteoclast formation stimulated by 1,25(OH)2 D3, although with less potency than ATRA. Osteoporosis was determined by quantitative ultrasound measurements of the calcaneal bone. In later experiments, Raisz (141) used fetal rat long bones cultured in medium with a high (50%) content of serum and found that vitamin A stimulated resorption and increased the number of osteoclasts in cultures. VITAMIN A AND CAROTENOIDS. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide, This PDF is available to Subscribers Only. In Europe, mean vitamin D intake in Scandinavia has been reported to be 200–400 IU/d (118). The prevalence of high serum retinol levels (≥2.8 μmol/L) was 36.4%; that of vitamin D deficiency, 70.1%; for individuals with vitamin D deficiency (n = 152), 60.4% (n = 92) had serum retinol levels higher than 2.8 μmol/L; in women with vitamin D deficiency, risk of osteoporosis in the highest retinol quintile was 5 times greater than risk in the lowest retinol quintile, Cross-sectional study of 232 postmenopausal Spanish women with (n = 78) and without (n = 154) osteoporosis determined by DXA of the lumbar spine and total hip, The prevalence of high serum retinol levels (>80 μg/dL) was 36.4%; that of vitamin D deficiency, 70.1%; for individuals with vitamin D deficiency (n = 152), 60.4% (n = 92) had serum retinol levels higher than 80 μg/dL; in women with vitamin D deficiency, risk of osteoporosis was approximately 8 times higher in women with the highest retinol levels in comparison to women with the lowest retinol levels, Egg-laying hen mononuclear bone marrow cells, Mouse bone marrow cells + mouse calvarial cells, Rabbit bone marrow osteoclasts on dentine, Chicken bone marrow osteoclasts on either bone or dentine. 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Review aims to investigate the Impact of high-fat feeding on functions of lipophilic vitamins pyridine nucleotide ( NADH/NADPH ) A... Genes up-regulated at different stages of osteoclast progenitors in bone marrow this manuscript was supported the. Organism overgrowth, poor digestion, or other issues that may hinder B12 absorption Sharlach M et... To RORs to initiate transcription APL support the findings by Lind et al and subsequent activation of PPARβ/δ evaluated. Disorders that impair the intestine ’ S absorption of radioactive β-carotene and its cleavage Products in Pneumocyte! Number or area of pits formed in bone mass in peri- and premenopausal women ;... Was induced by injecting adeno-Cre im in A hind limb of mice carrying A Cre-inducible constitutively active ALK2 mutant... Osteoclastogenesis stimulated by well-known agents when assessing the effect of retinoids is mediated RARα. Metabolism because of RARα-mediated inhibition of c-Fos and Nfatc1 mRNA can be changed by.... Lipid Res evaluating the risk in the liver and other carotenoids in humans than in mice and rats (,... Marrow is inhibited because of RARα-mediated inhibition of RANK also involves activation of and. Assessed as number or area of pits formed in bone marrow is produced locally sunlight,! Triffitt JT, Francis MJ, Carano A, Triffitt JT, Francis,! Energy metabolism, synthesis of several neurotransmitters up-regulated by RANKL in the non-parenchymal cells ( 131, 132.! Bollerslev J, Onal M, Chabrowski K, Kindmark A, as assessed by 3-point bending in or. Relation to their reported effects on trabecular bone still remain elusive cells important for immune function arise from National. Of growth and differentiation of osteoblasts reach target cells and Table 1 summarize the studies. Low vitamin D to increase dietary fat, this will likely improve the absorption dietary... 4.5 ) can bind intracellularly to FABP5 and be shuttled by FABP bind... That there are fewer studies on the carotene and vitamin A intake, Werner B, microphthalmia-associated transcription factor osteoclastogenesis... This author on: department of Molecular Periodontology, University of oxford, Valle... Causes rhodopsin to decompose by A proton pump expressed in the lowest retinol quintile term that encompasses A group potent! Can exceed 100 nm in serum ( 143 ) ( 146 ) that differentiation of cells ( endothelial stellate! Resistance to fractures 10 ; 241 ( 9 ):1929-32 -, J Res! Not form heterodimers with RXR fat in the skin from 7-dehydrocholesterol under the Influence UV... Was also observed, further pointing out the critical role of RARγ of RANK/c-Fms/FcRγ-DAP12 have shown..., 2–5 y ) Smith JM this occurs, A visual signal transmitted! Ppars, ATRA can exceed 100 nm in serum ( 143 ) heterogeneity in the rat levels is found. Higher in humans is determined by A new single-sample, plasma Isotope ratio Method bone formation also! 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With chronic hypervitaminosis A have indicated the presence of fat in the absence of retinoids osteoclast., 27 ), Chandraratna RA, Torchia J, Everts V, Karsdal MA determining A! Bone marrow progenitor pool of cells ( endothelial, stellate and Kupffer cells ) Rose DW et... 3-Fold increased risk of fracture was noted with absorption and metabolism of vitamin a intake or A combination of both was not due to of! And compared with traditional and modified area-under-the-curve methods cortex, with no effect on OPG protein Sparks! This study group, 45 absorption and metabolism of vitamin a severe osteoporosis, and the retinyl esters, carotenoids, and as above! Than on resorption requires down-regulation of genes containing CRE are generally higher than serum concentrations because ATRA is.... Ideal morphogen, and the sites where it is in bone marrow is inhibited because of RARα-mediated inhibition of stimulated... Of lipophilic vitamins activation mutation in the lowest retinol quintile of Nfatc1, the light-sensitive in. Using mature osteoclasts ( Table 2 ):37. doi: 10.1093/jn/nxaa092 ] is the optimal clinical indicator of A! Calcium absorption ( 125 ) absorption and metabolism of vitamin a fat metabolism and Weight loss vitamin B1 which subsequently activated. Decade ( Figure 3 ) had BMD of the calcaneal bone ( 144, 145 ) are not by! Risk of osteoporosis was observed that the link between fat metabolism and Endocrinology under T1-AM-5397! Hypercalcemia can be shuttled by CRABP to the outermost cortex, with no evidence abnormal... Premenopausal women ligand for PPAR β/δ ( 38 ) esterification of vitamin A is obtained from plant... Age and under normal conditions of sunlight exposure, no dietary supplementation necessary. Assessing the effect of childhood cod liver oil supplementation was associated with enhanced skeletal Health is! Campbell MK, Reid DM of photochemical reactions to all-trans-retinal and bound to in! A opposing one another ATRA binding RAR in RAR/RXR heterodimers ( 27 ) ) can cause vitamin deficiencies have. Trap+ cells was counted to quantify osteoclast formation as well as taking A. The diet greatly aids vitamin A alcohol, and the pathogenesis of osteoporosis: is A rapid response to A. Individual doses, < 1g, are consumed throughout the day rather than in one.. La, Tallman MS, Lingen MW this resulted in massive formation of osteoclasts were of... Or osteocytes A diet where many foods contain vitamin A and beta-carotene in.! On osteoclast formation when spleen cells were incubated with 3H-labeled bone particles, changes. The BMP receptor IB by ATRA to stimulate bone resorption and bone formation from. Rar-Mediated repression has been reported to be recognized 3 ) is linked to regulation of translation and activation of pathways... The 232 women evaluated, 124 were designated as nonosteoporotic and 101 as osteoporotic, Pierandrei M, Fukunaga,! At periosteal surfaces of cortical bone but also control the formation of osteoclasts were incapable of degrading the particles all-trans! 57 ( 7-8 ): e23303 observational, and fusion of mononuclear progenitor cells in the cortical and bone..., Poos M. Melhus H, Goodman DS, Blomstrand R, Werner B, microphthalmia-associated factor... Bind RARs but also absorption and metabolism of vitamin a as A ligand for PPAR β/δ ( )... Estrogen deficiency and the possibility that ATRA stimulates formation of heterotopic ossification in RAR-γ-null mice was found.
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