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Retinoid receptors in bone and their role in bone remodeling.

Henning P, Conaway HH, Lerner UH - Front Endocrinol (Lausanne) (2015)

Bottom Line: Some epidemiological studies have suggested that increased intake of vitamin A and increased serum levels of retinoids may decrease bone mineral density and increase fracture rate, but the literature on this is not conclusive.The current review summarizes how vitamin A is taken up by the intestine, metabolized, stored in the liver, and processed to ATRA.ATRA's effects on formation and activity of osteoclasts and osteoblasts are outlined, and a summary of clinical data pertaining to vitamin A and bone is presented.

View Article: PubMed Central - PubMed

Affiliation: Centre for Bone and Arthritis Research, Institute for Medicine, Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden.

ABSTRACT
Vitamin A (retinol) is a necessary and important constituent of the body which is provided by food intake of retinyl esters and carotenoids. Vitamin A is known best for being important for vision, but in addition to the eye, vitamin A is necessary in numerous other organs in the body, including the skeleton. Vitamin A is converted to an active compound, all-trans-retinoic acid (ATRA), which is responsible for most of its biological actions. ATRA binds to intracellular nuclear receptors called retinoic acid receptors (RARα, RARβ, RARγ). RARs and closely related retinoid X receptors (RXRα, RXRβ, RXRγ) form heterodimers which bind to DNA and function as ligand-activated transcription factors. It has been known for many years that hypervitaminosis A promotes skeleton fragility by increasing osteoclast formation and decreasing cortical bone mass. Some epidemiological studies have suggested that increased intake of vitamin A and increased serum levels of retinoids may decrease bone mineral density and increase fracture rate, but the literature on this is not conclusive. The current review summarizes how vitamin A is taken up by the intestine, metabolized, stored in the liver, and processed to ATRA. ATRA's effects on formation and activity of osteoclasts and osteoblasts are outlined, and a summary of clinical data pertaining to vitamin A and bone is presented.

No MeSH data available.


Related in: MedlinePlus

Retinoids reach target cells mainly in the form of retinol bound to RBP. A fraction of retinoids is also delivered by chylomicrons. Inside the cell, retinol is oxidized to the active metabolite ATRA by ADH and RALDH via all-trans-retinal that is bound by CRBP. ATRA is shuttled to the nucleus by CRABP and FABP, facilitating binding to RARs and PPARs, respectively. RARs and PPARs form heterodimers with RXRs to activate transcription. In addition, ATRA can bind to RORs to initiate transcription. Non-genomic effects of retinoids include phosphorylation of CREB that translocates to the nucleus and activates genes. ATRA is inactivated by oxidation by CYP26 enzymes.
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Figure 2: Retinoids reach target cells mainly in the form of retinol bound to RBP. A fraction of retinoids is also delivered by chylomicrons. Inside the cell, retinol is oxidized to the active metabolite ATRA by ADH and RALDH via all-trans-retinal that is bound by CRBP. ATRA is shuttled to the nucleus by CRABP and FABP, facilitating binding to RARs and PPARs, respectively. RARs and PPARs form heterodimers with RXRs to activate transcription. In addition, ATRA can bind to RORs to initiate transcription. Non-genomic effects of retinoids include phosphorylation of CREB that translocates to the nucleus and activates genes. ATRA is inactivated by oxidation by CYP26 enzymes.

Mentions: Retinoid in the form of all-trans retinol is transported from the liver to peripheral cells bound to RBP in plasma. In the fasting state, >95% of retinoid in the circulation is found as retinol bound to RBP. Approximately, 25–33% of dietary retinoid that is absorbed in the intestine is delivered to tissues other than the liver by chylomicrons (27). A transmembrane-spanning receptor stimulated by retinoic acid receptor (STRA6) mediates the cellular uptake of retinol from RBP, while hydrolysis of retinyl esters by lipoprotein lipase is thought to facilitate uptake of retinol from chylomicrons (29, 30) (Figure 2). Carotenoids associated with lipoproteins in chylomicrons can be taken up by lipoprotein-specific receptors and converted to retinaldehyde (RALD) by β-caroten-15,15′-monooxygenase (BCMO1) (31). Bone is the second most important organ for clearance of chylomicron remnants, and it has been reported that other fat soluble vitamins can be delivered to osteoblasts in vivo via chylomicrons (32). Additionally, the active metabolite all-trans-retinoic acid (ATRA) is present at low levels in serum bound to albumin and has been shown to contribute to tissue levels of ATRA (33).


Retinoid receptors in bone and their role in bone remodeling.

Henning P, Conaway HH, Lerner UH - Front Endocrinol (Lausanne) (2015)

Retinoids reach target cells mainly in the form of retinol bound to RBP. A fraction of retinoids is also delivered by chylomicrons. Inside the cell, retinol is oxidized to the active metabolite ATRA by ADH and RALDH via all-trans-retinal that is bound by CRBP. ATRA is shuttled to the nucleus by CRABP and FABP, facilitating binding to RARs and PPARs, respectively. RARs and PPARs form heterodimers with RXRs to activate transcription. In addition, ATRA can bind to RORs to initiate transcription. Non-genomic effects of retinoids include phosphorylation of CREB that translocates to the nucleus and activates genes. ATRA is inactivated by oxidation by CYP26 enzymes.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4356160&req=5

Figure 2: Retinoids reach target cells mainly in the form of retinol bound to RBP. A fraction of retinoids is also delivered by chylomicrons. Inside the cell, retinol is oxidized to the active metabolite ATRA by ADH and RALDH via all-trans-retinal that is bound by CRBP. ATRA is shuttled to the nucleus by CRABP and FABP, facilitating binding to RARs and PPARs, respectively. RARs and PPARs form heterodimers with RXRs to activate transcription. In addition, ATRA can bind to RORs to initiate transcription. Non-genomic effects of retinoids include phosphorylation of CREB that translocates to the nucleus and activates genes. ATRA is inactivated by oxidation by CYP26 enzymes.
Mentions: Retinoid in the form of all-trans retinol is transported from the liver to peripheral cells bound to RBP in plasma. In the fasting state, >95% of retinoid in the circulation is found as retinol bound to RBP. Approximately, 25–33% of dietary retinoid that is absorbed in the intestine is delivered to tissues other than the liver by chylomicrons (27). A transmembrane-spanning receptor stimulated by retinoic acid receptor (STRA6) mediates the cellular uptake of retinol from RBP, while hydrolysis of retinyl esters by lipoprotein lipase is thought to facilitate uptake of retinol from chylomicrons (29, 30) (Figure 2). Carotenoids associated with lipoproteins in chylomicrons can be taken up by lipoprotein-specific receptors and converted to retinaldehyde (RALD) by β-caroten-15,15′-monooxygenase (BCMO1) (31). Bone is the second most important organ for clearance of chylomicron remnants, and it has been reported that other fat soluble vitamins can be delivered to osteoblasts in vivo via chylomicrons (32). Additionally, the active metabolite all-trans-retinoic acid (ATRA) is present at low levels in serum bound to albumin and has been shown to contribute to tissue levels of ATRA (33).

Bottom Line: Some epidemiological studies have suggested that increased intake of vitamin A and increased serum levels of retinoids may decrease bone mineral density and increase fracture rate, but the literature on this is not conclusive.The current review summarizes how vitamin A is taken up by the intestine, metabolized, stored in the liver, and processed to ATRA.ATRA's effects on formation and activity of osteoclasts and osteoblasts are outlined, and a summary of clinical data pertaining to vitamin A and bone is presented.

View Article: PubMed Central - PubMed

Affiliation: Centre for Bone and Arthritis Research, Institute for Medicine, Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden.

ABSTRACT
Vitamin A (retinol) is a necessary and important constituent of the body which is provided by food intake of retinyl esters and carotenoids. Vitamin A is known best for being important for vision, but in addition to the eye, vitamin A is necessary in numerous other organs in the body, including the skeleton. Vitamin A is converted to an active compound, all-trans-retinoic acid (ATRA), which is responsible for most of its biological actions. ATRA binds to intracellular nuclear receptors called retinoic acid receptors (RARα, RARβ, RARγ). RARs and closely related retinoid X receptors (RXRα, RXRβ, RXRγ) form heterodimers which bind to DNA and function as ligand-activated transcription factors. It has been known for many years that hypervitaminosis A promotes skeleton fragility by increasing osteoclast formation and decreasing cortical bone mass. Some epidemiological studies have suggested that increased intake of vitamin A and increased serum levels of retinoids may decrease bone mineral density and increase fracture rate, but the literature on this is not conclusive. The current review summarizes how vitamin A is taken up by the intestine, metabolized, stored in the liver, and processed to ATRA. ATRA's effects on formation and activity of osteoclasts and osteoblasts are outlined, and a summary of clinical data pertaining to vitamin A and bone is presented.

No MeSH data available.


Related in: MedlinePlus