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Article: Skeletal phenotype of the leptin receptor-deficient db/db mouse

TitleSkeletal phenotype of the leptin receptor-deficient db/db mouse
Authors
Issue Date2011
PublisherAmerican Society for Bone and Mineral Research. The Journal's web site is located at http://www.jbmr.org/view/0/index.html
Citation
Journal of Bone and Mineral Research, 2011, v. 26 n. 8, p. 1698-1709 How to Cite?
AbstractLeptin, a major hormonal product of the adipocyte, regulates appetite and reproductive function through its hypothalamic receptors. The leptin receptor is present in osteoblasts and chondrocytes, and previously we have shown leptin to be an anabolic bone factor in vitro, stimulating osteoblast proliferation and inhibiting osteoclastogenesis. Leptin increases bone mass and reduces bone fragility when administered peripherally but also can indirectly reduce bone mass when administered into the central nervous system. However, data from animal models deficient in either leptin (ob/ob) or its receptor (db/db) remain contradictory. We compared the bone phenotype of leptin receptor-deficient (db/db) and wild-type mice using micro-computed tomographic (microCT) analysis of the proximal tibias and vertebrae. In the tibia, db/db mice had reduced percent trabecular bone volume (13.0 +/- 1.62% in wild-type versus 6.01 +/- 0.601% in db/db mice, p = .002) and cortical bone volume (411 +/- 21.5 microm(3) versus 316 +/- 3.53 microm(3), p = .0014), trabecular thickness (48.4 +/- 001.07 microm versus 45.1 +/- 0.929 microm, p = .041) and trabecular number (2.68 +/- 0.319 mm(-1) versus 1.34 +/- 0.148 mm(-1), p = .0034). In the fifth lumbar vertebral body, the trabecular thickness and cortical thickness were decreased in the db/db versus wild-type mice (0.053 +/- 0.0011 mm versus 0.047 +/- 0.0013 mm, p = .0002 and 0.062 +/- 0.00054 mm versus 0.056 +/- 0.0009 mm, p = .0001), respectively, whereas the trabecular and cortical percent bone volume and trabecular number did not reach significance. The total (endosteal and periosteal) cortical perimeter (12.2 +/- 0.19 mm versus 13.2 +/- 0.30 mm, p = .01) was increased. The serum osteocalcin levels were reduced in the db/db mice, suggesting that bone formation rates are decreased. The material properties of db/db femurs were determined by three-point bending and nanoindentation, showing decreased bone strength (13.3 +/- 0.280 N versus 7.99 +/- 0.984 N, p = .0074) and material stiffness (28.5 +/- 0.280 GPa versus 25.8 +/- 0.281 GPa, p < .0001). These results demonstrate that bone mass and strength are reduced in the absence of leptin signaling, indicating that leptin acts in vivo as an anabolic bone factor. This concurs with results of in vitro studies and of peripheral leptin administration in vivo and suggests that leptin's direct effects on bone cells are likely to override its actions via the central nervous system.
Persistent Identifierhttp://hdl.handle.net/10722/139603
ISSN
2015 Impact Factor: 5.622
2015 SCImago Journal Rankings: 2.773
ISI Accession Number ID
Funding AgencyGrant Number
Health Research Council of New Zealand
Funding Information:

Funding for the work was provided by the Health Research Council of New Zealand.

 

DC FieldValueLanguage
dc.contributor.authorWilliams, GAen_US
dc.contributor.authorCallon, KEen_US
dc.contributor.authorWatson, Men_US
dc.contributor.authorCosta, JLen_US
dc.contributor.authorDing, Yen_US
dc.contributor.authorDickinson, Men_US
dc.contributor.authorWang, Yen_US
dc.contributor.authorNaot, Den_US
dc.contributor.authorReid, IRen_US
dc.contributor.authorCornish, J-
dc.date.accessioned2011-09-23T05:52:27Z-
dc.date.available2011-09-23T05:52:27Z-
dc.date.issued2011en_US
dc.identifier.citationJournal of Bone and Mineral Research, 2011, v. 26 n. 8, p. 1698-1709en_US
dc.identifier.issn0884-0431-
dc.identifier.urihttp://hdl.handle.net/10722/139603-
dc.description.abstractLeptin, a major hormonal product of the adipocyte, regulates appetite and reproductive function through its hypothalamic receptors. The leptin receptor is present in osteoblasts and chondrocytes, and previously we have shown leptin to be an anabolic bone factor in vitro, stimulating osteoblast proliferation and inhibiting osteoclastogenesis. Leptin increases bone mass and reduces bone fragility when administered peripherally but also can indirectly reduce bone mass when administered into the central nervous system. However, data from animal models deficient in either leptin (ob/ob) or its receptor (db/db) remain contradictory. We compared the bone phenotype of leptin receptor-deficient (db/db) and wild-type mice using micro-computed tomographic (microCT) analysis of the proximal tibias and vertebrae. In the tibia, db/db mice had reduced percent trabecular bone volume (13.0 +/- 1.62% in wild-type versus 6.01 +/- 0.601% in db/db mice, p = .002) and cortical bone volume (411 +/- 21.5 microm(3) versus 316 +/- 3.53 microm(3), p = .0014), trabecular thickness (48.4 +/- 001.07 microm versus 45.1 +/- 0.929 microm, p = .041) and trabecular number (2.68 +/- 0.319 mm(-1) versus 1.34 +/- 0.148 mm(-1), p = .0034). In the fifth lumbar vertebral body, the trabecular thickness and cortical thickness were decreased in the db/db versus wild-type mice (0.053 +/- 0.0011 mm versus 0.047 +/- 0.0013 mm, p = .0002 and 0.062 +/- 0.00054 mm versus 0.056 +/- 0.0009 mm, p = .0001), respectively, whereas the trabecular and cortical percent bone volume and trabecular number did not reach significance. The total (endosteal and periosteal) cortical perimeter (12.2 +/- 0.19 mm versus 13.2 +/- 0.30 mm, p = .01) was increased. The serum osteocalcin levels were reduced in the db/db mice, suggesting that bone formation rates are decreased. The material properties of db/db femurs were determined by three-point bending and nanoindentation, showing decreased bone strength (13.3 +/- 0.280 N versus 7.99 +/- 0.984 N, p = .0074) and material stiffness (28.5 +/- 0.280 GPa versus 25.8 +/- 0.281 GPa, p < .0001). These results demonstrate that bone mass and strength are reduced in the absence of leptin signaling, indicating that leptin acts in vivo as an anabolic bone factor. This concurs with results of in vitro studies and of peripheral leptin administration in vivo and suggests that leptin's direct effects on bone cells are likely to override its actions via the central nervous system.-
dc.languageengen_US
dc.publisherAmerican Society for Bone and Mineral Research. The Journal's web site is located at http://www.jbmr.org/view/0/index.html-
dc.relation.ispartofJournal of Bone and Mineral Researchen_US
dc.subject.meshBone and Bones - pathology - radiography-
dc.subject.meshFemur - pathology - radiography-
dc.subject.meshMice, Mutant Strains-
dc.subject.meshPhenotype-
dc.subject.meshReceptors, Leptin - deficiency - metabolism-
dc.titleSkeletal phenotype of the leptin receptor-deficient db/db mouseen_US
dc.typeArticleen_US
dc.identifier.emailWang, Y: yuwanghk@hku.hken_US
dc.identifier.authorityWang, Y=rp00239en_US
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1002/jbmr.367-
dc.identifier.pmid21328476-
dc.identifier.scopuseid_2-s2.0-79957921143-
dc.identifier.hkuros195685en_US
dc.identifier.volume26en_US
dc.identifier.issue8-
dc.identifier.spage1698en_US
dc.identifier.epage1709en_US
dc.identifier.isiWOS:000293382600003-
dc.publisher.placeUnited States-
dc.identifier.f100013032956-

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