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Retinoids stimulate...
Retinoids stimulate periosteal bone resorption by enhancing the protein RANKL, a response inhibited by monomeric glucocorticoid receptor.
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- Conaway, H Herschel (author)
- Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, Arkansas
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- Pirhayati, Amir (author)
- Umeå universitet,Molekylär paradontologi
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- Persson, Emma (author)
- Umeå universitet,Molekylär paradontologi
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- Pettersson, Ulrika (author)
- Umeå universitet,Klinisk farmakologi
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- Svensson, Olle (author)
- Umeå universitet,Kirurgi
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- Lindholm, Catharina, 1967 (author)
- Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research,Institutionen för medicin,Institute of Medicine,Center for Bone and Arthritis Research at the Institute for Medicine, Sahlgrenska Academy at the University of Gothenburg
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- Henning, Petra, 1974 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin,Centre for Bone and Arthritis Research,Institute of Medicine,Center for Bone and Arthritis Research at the Institute for Medicine, Sahlgrenska Academy at the University of Gothenburg
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- Tuckermann, Jan (author)
- Tissue-specific Hormone Action, Leibniz Institute for Age Research, Fritz Lipmann Institute, D-07745 Jena, Germany
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- Lerner, Ulf H (author)
- Umeå universitet,Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research,Institutionen för medicin, avdelningen för invärtesmedicin,Institute of Medicine, Department of Internal Medicine,Molekylär paradontologi
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(creator_code:org_t)
- 2011
- 2011
- English.
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In: The Journal of biological chemistry. - 1083-351X .- 0021-9258. ; 286:36, s. 31425-36
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Abstract
Subject headings
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- Increased vitamin A (retinol) intake has been suggested to increase bone fragility. In the present study, we investigated effects of retinoids on bone resorption in cultured neonatal mouse calvarial bones and their interaction with glucocorticoids (GC). All-trans-retinoic acid (ATRA), retinol, retinalaldehyde, and 9-cis-retinoic acid stimulated release of (45)Ca from calvarial bones. The resorptive effect of ATRA was characterized by mRNA expression of genes associated with osteoclast differentiation, enhanced osteoclast number, and bone matrix degradation. In addition, the RANKL/OPG ratio was increased by ATRA, release of (45)Ca stimulated by ATRA was blocked by exogenous OPG, and mRNA expression of genes associated with bone formation was decreased by ATRA. All retinoid acid receptors (RARα/β/γ) were expressed in calvarial bones. Agonists with affinity to all receptor subtypes or specifically to RARα enhanced the release of (45)Ca and mRNA expression of Rankl, whereas agonists with affinity to RARβ/γ or RARγ had no effects. Stimulation of Rankl mRNA by ATRA was competitively inhibited by the RARα antagonist GR110. Exposure of calvarial bones to GC inhibited the stimulatory effects of ATRA on (45)Ca release and Rankl mRNA and protein expression. This inhibitory effect was reversed by the glucocorticoid receptor (GR) antagonist RU 486. Increased Rankl mRNA stimulated by ATRA was also blocked by GC in calvarial bones from mice with a GR mutation that blocks dimerization (GR(dim) mice). The data suggest that ATRA enhances periosteal bone resorption by increasing the RANKL/OPG ratio via RARα receptors, a response that can be inhibited by monomeric GR.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Keyword
- Animals
- Animals
- Newborn
- Bone Resorption
- chemically induced
- Mice
- Osteoprotegerin
- Periosteum
- pathology
- RANK Ligand
- agonists
- antagonists & inhibitors
- Receptors
- Glucocorticoid
- physiology
- Receptors
- Retinoic Acid
- Retinoids
- pharmacology
- Tretinoin
- pharmacology
Publication and Content Type
- ref (subject category)
- art (subject category)
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Conaway, H Hersc ...
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Pirhayati, Amir
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Persson, Emma
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Pettersson, Ulri ...
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Svensson, Olle
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Lindholm, Cathar ...
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Henning, Petra, ...
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Tuckermann, Jan
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Lerner, Ulf H
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and Endocrinology an ...
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NATURAL SCIENCES
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University of Gothenburg
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Umeå University