Sclerostin does not play a major role in the pathogenesis of skeletal complications in type 2 diabetes mellitus
Identifieur interne : 001761 ( Main/Exploration ); précédent : 001760; suivant : 001762Sclerostin does not play a major role in the pathogenesis of skeletal complications in type 2 diabetes mellitus
Auteurs : M. Pereira ; S. Gohin ; N. Lund ; A. Hvid ; P. J. Smitham [Royaume-Uni, Australie] ; M. J. Oddy [Royaume-Uni] ; I. Reichert [Royaume-Uni] ; D. Farlay [France] ; J. P. Roux [France] ; M. E. Cleasby ; C. ChenuSource :
- Osteoporosis International [ 0937-941X ] ; 2016.
Abstract
In contrast to previously reported elevations in serum sclerostin levels in diabetic patients, the present study shows that the impaired bone microarchitecture and cellular turnover associated with type 2 diabetes mellitus (T2DM)-like conditions in ZDF rats are not correlated with changes in serum and bone sclerostin expression.
T2DM is associated with impaired skeletal structure and a higher prevalence of bone fractures. Sclerostin, a negative regulator of bone formation, is elevated in serum of diabetic patients. We aimed to relate changes in bone architecture and cellular activities to sclerostin production in the Zucker diabetic fatty (ZDF) rat.
Bone density and architecture were measured by micro-CT and bone remodelling by histomorphometry in tibiae and femurs of 14-week-old male ZDF rats and lean Zucker controls (
ZDF rats showed lower trabecular bone mineral density and bone mass compared to controls, due to decreases in bone volume and thickness, along with impaired bone connectivity and cortical bone geometry. Bone remodelling was impaired in diabetic rats, demonstrated by decreased bone formation rate and increased percentage of tartrate-resistant acid phosphatase-positive osteoclastic surfaces. Serum sclerostin levels (ELISA) were higher in ZDF compared to lean rats at 9 weeks (+40 %,
T2DM results in impaired skeletal architecture through altered remodelling pathways, but despite altered serum levels, it does not appear that sclerostin contributes to the deleterious effect of T2DM in rat bone.
Url:
DOI: 10.1007/s00198-016-3718-0
PubMed: 27468901
PubMed Central: 5206261
Affiliations:
- Australie, France, Royaume-Uni
- Angleterre, Auvergne-Rhône-Alpes, Grand Londres, Rhône-Alpes
- Londres, Lyon
- University College de Londres
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Pereira</name><affiliation><nlm:aff id="Aff1">Department of Comparative Biomedical sciences, Royal Veterinary College, Royal College Street, London, NW1 0TU UK</nlm:aff><wicri:noCountry code="subfield">NW1 0TU UK</wicri:noCountry></affiliation></author><author><name sortKey="Gohin, S" sort="Gohin, S" uniqKey="Gohin S" first="S." last="Gohin">S. Gohin</name><affiliation><nlm:aff id="Aff1">Department of Comparative Biomedical sciences, Royal Veterinary College, Royal College Street, London, NW1 0TU UK</nlm:aff><wicri:noCountry code="subfield">NW1 0TU UK</wicri:noCountry></affiliation></author><author><name sortKey="Lund, N" sort="Lund, N" uniqKey="Lund N" first="N." last="Lund">N. Lund</name><affiliation><nlm:aff id="Aff1">Department of Comparative Biomedical sciences, Royal Veterinary College, Royal College Street, London, NW1 0TU UK</nlm:aff><wicri:noCountry code="subfield">NW1 0TU UK</wicri:noCountry></affiliation></author><author><name sortKey="Hvid, A" sort="Hvid, A" uniqKey="Hvid A" first="A." last="Hvid">A. Hvid</name><affiliation><nlm:aff id="Aff1">Department of Comparative Biomedical sciences, Royal Veterinary College, Royal College Street, London, NW1 0TU UK</nlm:aff><wicri:noCountry code="subfield">NW1 0TU UK</wicri:noCountry></affiliation></author><author><name sortKey="Smitham, P J" sort="Smitham, P J" uniqKey="Smitham P" first="P. J." last="Smitham">P. J. Smitham</name><affiliation wicri:level="4"><nlm:aff id="Aff2">University College London, London, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>University College London, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region><settlement type="city">Londres</settlement></placeName><orgName type="university">University College de Londres</orgName></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff4">The University of Adelaide, Adelaide, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>The University of Adelaide, Adelaide</wicri:regionArea><wicri:noRegion>Adelaide</wicri:noRegion></affiliation></author><author><name sortKey="Oddy, M J" sort="Oddy, M J" uniqKey="Oddy M" first="M. J." last="Oddy">M. J. Oddy</name><affiliation wicri:level="3"><nlm:aff id="Aff3">University College Hospital, London, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>University College Hospital, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Reichert, I" sort="Reichert, I" uniqKey="Reichert I" first="I." last="Reichert">I. Reichert</name><affiliation wicri:level="3"><nlm:aff id="Aff5">Kings College London, London, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Kings College London, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Farlay, D" sort="Farlay, D" uniqKey="Farlay D" first="D." last="Farlay">D. Farlay</name><affiliation wicri:level="3"><nlm:aff id="Aff6">INSERM UMR1033 and Université de Lyon, Lyon, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM UMR1033 and Université de Lyon, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Roux, J P" sort="Roux, J P" uniqKey="Roux J" first="J. P." last="Roux">J. P. Roux</name><affiliation wicri:level="3"><nlm:aff id="Aff6">INSERM UMR1033 and Université de Lyon, Lyon, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM UMR1033 and Université de Lyon, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Cleasby, M E" sort="Cleasby, M E" uniqKey="Cleasby M" first="M. E." last="Cleasby">M. E. Cleasby</name><affiliation><nlm:aff id="Aff1">Department of Comparative Biomedical sciences, Royal Veterinary College, Royal College Street, London, NW1 0TU UK</nlm:aff><wicri:noCountry code="subfield">NW1 0TU UK</wicri:noCountry></affiliation></author><author><name sortKey="Chenu, C" sort="Chenu, C" uniqKey="Chenu C" first="C." last="Chenu">C. Chenu</name><affiliation><nlm:aff id="Aff1">Department of Comparative Biomedical sciences, Royal Veterinary College, Royal College Street, London, NW1 0TU UK</nlm:aff><wicri:noCountry code="subfield">NW1 0TU UK</wicri:noCountry></affiliation></author></analytic><series><title level="j">Osteoporosis International</title><idno type="ISSN">0937-941X</idno><idno type="eISSN">1433-2965</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Summary</title><p>In contrast to previously reported elevations in serum sclerostin levels in diabetic patients, the present study shows that the impaired bone microarchitecture and cellular turnover associated with type 2 diabetes mellitus (T2DM)-like conditions in ZDF rats are not correlated with changes in serum and bone sclerostin expression.</p></sec><sec><title>Introduction</title><p>T2DM is associated with impaired skeletal structure and a higher prevalence of bone fractures. Sclerostin, a negative regulator of bone formation, is elevated in serum of diabetic patients. We aimed to relate changes in bone architecture and cellular activities to sclerostin production in the Zucker diabetic fatty (ZDF) rat.</p></sec><sec><title>Methods</title><p>Bone density and architecture were measured by micro-CT and bone remodelling by histomorphometry in tibiae and femurs of 14-week-old male ZDF rats and lean Zucker controls (<italic>n</italic> = 6/group).</p></sec><sec><title>Results</title><p>ZDF rats showed lower trabecular bone mineral density and bone mass compared to controls, due to decreases in bone volume and thickness, along with impaired bone connectivity and cortical bone geometry. Bone remodelling was impaired in diabetic rats, demonstrated by decreased bone formation rate and increased percentage of tartrate-resistant acid phosphatase-positive osteoclastic surfaces. Serum sclerostin levels (ELISA) were higher in ZDF compared to lean rats at 9 weeks (+40 %, <italic>p</italic> < 0.01), but this difference disappeared as their glucose control deteriorated and by week 14, ZDF rats had lower sclerostin levels than control rats (−44 %, <italic>p</italic> < 0.0001). Bone sclerostin mRNA (qPCR) and protein (immunohistochemistry) were similar in ZDF, and lean rats at 14 weeks and genotype did not affect the number of empty osteocytic lacunae in cortical and trabecular bone.</p></sec><sec><title>Conclusion</title><p>T2DM results in impaired skeletal architecture through altered remodelling pathways, but despite altered serum levels, it does not appear that sclerostin contributes to the deleterious effect of T2DM in rat bone.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Yamamoto, M" uniqKey="Yamamoto M">M Yamamoto</name></author><author><name sortKey="Yamaguchi, T" uniqKey="Yamaguchi T">T Yamaguchi</name></author><author><name sortKey="Yamauchi, M" uniqKey="Yamauchi M">M Yamauchi</name></author><author><name sortKey="Kaji, H" uniqKey="Kaji H">H Kaji</name></author><author><name sortKey="Sugimoto, T" uniqKey="Sugimoto T">T 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de Londres</li></orgName></list><tree><noCountry><name sortKey="Chenu, C" sort="Chenu, C" uniqKey="Chenu C" first="C." last="Chenu">C. Chenu</name><name sortKey="Cleasby, M E" sort="Cleasby, M E" uniqKey="Cleasby M" first="M. E." last="Cleasby">M. E. Cleasby</name><name sortKey="Gohin, S" sort="Gohin, S" uniqKey="Gohin S" first="S." last="Gohin">S. Gohin</name><name sortKey="Hvid, A" sort="Hvid, A" uniqKey="Hvid A" first="A." last="Hvid">A. Hvid</name><name sortKey="Lund, N" sort="Lund, N" uniqKey="Lund N" first="N." last="Lund">N. Lund</name><name sortKey="Pereira, M" sort="Pereira, M" uniqKey="Pereira M" first="M." last="Pereira">M. Pereira</name></noCountry><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Smitham, P J" sort="Smitham, P J" uniqKey="Smitham P" first="P. J." last="Smitham">P. J. Smitham</name></region><name sortKey="Oddy, M J" sort="Oddy, M J" uniqKey="Oddy M" first="M. J." last="Oddy">M. J. Oddy</name><name sortKey="Reichert, I" sort="Reichert, I" uniqKey="Reichert I" first="I." last="Reichert">I. Reichert</name></country><country name="Australie"><noRegion><name sortKey="Smitham, P J" sort="Smitham, P J" uniqKey="Smitham P" first="P. J." last="Smitham">P. J. Smitham</name></noRegion></country><country name="France"><region name="Auvergne-Rhône-Alpes"><name sortKey="Farlay, D" sort="Farlay, D" uniqKey="Farlay D" first="D." last="Farlay">D. Farlay</name></region><name sortKey="Roux, J P" sort="Roux, J P" uniqKey="Roux J" first="J. P." last="Roux">J. P. Roux</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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