title: Histological assessment for femora of ovariectomized obesity (db/db) mice carrying mutated leptin receptor.
abstract: In order to provide a clue to understand the interplay between leptin and estrogen, we have examined femoral metaphyses of ovariectomized db/db mice carrying a mutated leptin receptor. We performed ovariectomy (OVX) or sham-operation (sham) on 12-week old female wild-type and db/db mice, and then, after 8 weeks, divided the animals into four groups: wild-type sham, wild-type OVX, db/db sham and db/db OVX. Samples from all groups were prepared for histochemical and ultrastructural examinations. As a result, db/db sham mice showed a reduced number and thickness of metaphyseal trabeculae and excessive adipose tissue when compared to wild-type sham mice. The wild-type OVX group exhibited markedly diminished trabecular number, as well as lower populations of osteoblasts and osteoclasts in comparison to wild-type sham group. On the other hand, trabecular numbers were similar for the two db/db groups, suggesting that the effect of the ovariectomy, i.e., estrogen deficiency may be lessened in this animal model. Leptin receptor was mainly found in osteoblasts and in bone marrow stromal cells including adipocytes. In addition, the expression of estrogen receptor did not seem to change after OVX in wild-type mice and in db/db mice. Both db/db sham and OVX mice featured many adipocytes close to the metaphyseal chondro-osseous junction, while osteoblasts accumulated glycogen granules and lipid droplets. Therefore, it seems likely that the disruption of leptin signaling in db/db mice shifts the cell differentiation cascade towards the adipocyte lineage, resulting in an osteoporotic bone independently of estrogen deficiency.
authors.affiliation: Department of Developmental Biology of Hard Tissue, Graduate School of Dental Medicine, Hokkaido University, Sapporo, Japan.|Department of Oral and Maxillofacial Surgery, Graduate School of Dental Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Department of Developmental Biology of Hard Tissue, Graduate School of Dental Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Tomoka
authors.initials: T
authors.lastname: Hasegawa
authors.affiliation: Department of Developmental Biology of Hard Tissue, Graduate School of Dental Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Tamaki
authors.initials: T
authors.lastname: Yamada
authors.affiliation: Department of Developmental Biology of Hard Tissue, Graduate School of Dental Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Tomomaya
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Department of Developmental Biology of Hard Tissue, Graduate School of Dental Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Muneteru
authors.initials: M
authors.lastname: Sasaki
authors.affiliation: Department of Developmental Biology of Hard Tissue, Graduate School of Dental Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Hongo
authors.affiliation: Department of Developmental Biology of Hard Tissue, Graduate School of Dental Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Kanako
authors.initials: K
authors.lastname: Tsuboi
authors.affiliation: Department of Developmental Biology of Hard Tissue, Graduate School of Dental Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Haraguchi
authors.affiliation: Dental School, Federal University of Sergipe at Lagarto, Aracaju, Brazil.
authors.forename: Paulo Henrique Luiz
authors.initials: PH
authors.lastname: de Freitas
authors.affiliation: Shandong Provincial Key Laboratory of Oral Biomedicine, The School of Stomatology, Shandong University, Jinan, China.
authors.forename: Minqi
authors.initials: M
authors.lastname: Li
authors.affiliation: Division of Biochemistry, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Kimimitsu
authors.initials: K
authors.lastname: Oda
authors.affiliation: Department of Oral and Maxillofacial Surgery, Graduate School of Dental Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Totsuka
authors.affiliation: Department of Oral and Maxillofacial Surgery, Graduate School of Dental Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Kanchu
authors.initials: K
authors.lastname: Tei
authors.affiliation: Department of Developmental Biology of Hard Tissue, Graduate School of Dental Medicine, Hokkaido University, Sapporo, Japan. amizuka@den.hokudai.ac.jp.
authors.forename: Norio
authors.initials: N
authors.lastname: Amizuka
mesh_terms: D000273:Adipose Tissue / Q000473:pathology; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005269:Femur / Q000473:pathology*; D051379:Mice; D008817:Mice, Mutant Strains; D046529:Microscopy, Electron, Transmission; D009765:Obesity / Q000503:physiopathology*; D010024:Osteoporosis / Q000473:pathology / Q000503:physiopathology*; D010052:Ovariectomy; D016133:Polymerase Chain Reaction; D054411:Receptors, Leptin / Q000235:genetics* / Q000378:metabolism; D059467:Transcriptome
chemical_list: D054411:Receptors, Leptin; C515447:leptin receptor, mouse