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High dietary intake...
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Lind, ThomasUppsala universitet,Klinisk farmakologi,Clinical pharmacogenetics and osteoporosis
(författare)
High dietary intake of retinol leads to bone marrow hypoxia and diaphyseal endosteal mineralization in rats
- Artikel/kapitelEngelska2011
Förlag, utgivningsår, omfång ...
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Elsevier BV,2011
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printrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:uu-133794
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-133794URI
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https://doi.org/10.1016/j.bone.2010.10.169DOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:122213287URI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:art swepub-publicationtype
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Correction in: Bone, vol. 50, issue 5, page 1205DOI: 10.1016/j.bone.2012.02.016
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Vitamin A (retinol) is the only molecule known to induce spontaneous fractures in laboratory animals and we have identified retinol as a risk factor for fracture in humans. Since subsequent observational studies in humans and old animal data both show that high retinol intake appears to only have small effects on bone mineral density (BMD) we undertook a mechanistic study of how excess retinol reduces bone diameter while leaving BMD essentially unaffected. We fed growing rats high doses of retinol for only 1week. Bone analysis involved antibody-based methods, histology, pQCT, biomechanics and bone compartment-specific PCR together with Fourier Transform Infrared Spectroscopy of bone mineral. Excess dietary retinol induced weakening of bones with little apparent effect on BMD. Periosteal osteoclasts increased but unexpectedly endosteal osteoclasts disappeared and there was a reduction of osteoclastic serum markers. There was also a lack of capillary erythrocytes, endothelial cells and serum retinol transport protein in the endosteal/marrow compartment. A further indication of reduced endosteal/marrow blood flow was the increased expression of hypoxia-associated genes. Also, in contrast to the inhibitory effects in vitro, the marrow of retinol-treated rats showed increased expression of osteogenic genes. Finally, we show that hypervitaminotic bones have a higher degree of mineralization, which is in line with biomechanical data of preserved stiffness in spite of thinner bones. Together these novel findings suggest that a rapid primary effect of excess retinol on bone tissue is the impairment of endosteal/marrow blood flow leading to hypoxia and pathological endosteal mineralization.
Ämnesord och genrebeteckningar
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Bone mineralization
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Nutrition
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Osteoporosis
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Retinol
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Rodent
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MEDICINE
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MEDICIN
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Lind, MonicaUppsala universitet,Arbets- och miljömedicin,Eva Vingård(Swepub:uu)monilind
(författare)
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Jacobson, AnnicaUppsala universitet,Klinisk farmakologi,Clinical pharmacogenetics and osteoporosis(Swepub:uu)annijaco
(författare)
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Hu, LijuanUppsala universitet,Klinisk farmakologi,Clinical pharmacogenetics and osteoporosis
(författare)
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Sundqvist, AndersUppsala universitet,Klinisk farmakologi,Clinical pharmacogenetics and osteoporosis
(författare)
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Risteli, Juha
(författare)
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Yebra-Rodriguez, Africa
(författare)
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Larsson, SuneUppsala universitet,Ortopedi(Swepub:uu)sunelars
(författare)
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Rodriguez-Navarro, Alejandro
(författare)
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Andersson, GöranKarolinska Institutet
(författare)
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Melhus, HåkanUppsala universitet,Klinisk farmakologi,Clinical pharmacogenetics and osteoporosis(Swepub:uu)hakamelh
(författare)
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Uppsala universitetKlinisk farmakologi
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Bone: Elsevier BV48:3, s. 496-5068756-32821873-2763
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Lind, Thomas
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Lind, Monica
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Jacobson, Annica
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Hu, Lijuan
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Sundqvist, Ander ...
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Risteli, Juha
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visa fler...
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Yebra-Rodriguez, ...
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Larsson, Sune
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Rodriguez-Navarr ...
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Andersson, Göran
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Melhus, Håkan
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visa färre...
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Uppsala universitet
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Karolinska Institutet