Lef1 Haploinsufficient Mice Display a Low Turnover and Low Bone Mass Phenotype in a Gender- and Age-Specific Manner
| Autor: | Tomoyo Sasaki, Yang Chai, Braden Criswell, Eran Segev, Archana Tank, Yunfan Shi, Baruch Frenkel, Ralph Müller, Joseph Tam, Christopher Lee, Yankel Gabet, Thomas Kohler, Itai Bab, Tommy Noh, Jon Cogan, Elisheva Smith, James R. Woodgett, Lisa Kockeritz, Alexis Dixon |
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| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Male
Bone density lcsh:Medicine Diabetes and Endocrinology/Bone and Mineral Metabolism Bone remodeling Glycogen Synthase Kinase 3 Mice 0302 clinical medicine Bone Density lcsh:Science Receptor Mice Knockout 0303 health sciences Multidisciplinary Wnt signaling pathway Age Factors Osteoblast Rheumatology/Bone and Mineral Metabolism medicine.anatomical_structure Phenotype Receptors Androgen 030220 oncology & carcinogenesis embryonic structures Female Bone Remodeling Haploinsufficiency Research Article Signal Transduction medicine.medical_specialty Heterozygote Lymphoid Enhancer-Binding Factor 1 Biology Bone and Bones 03 medical and health sciences Sex Factors Internal medicine medicine Animals RNA Messenger 030304 developmental biology DNA Primers Glycogen Synthase Kinase 3 beta Base Sequence Physiology/Endocrinology lcsh:R Heterozygote advantage Mice Mutant Strains Androgen receptor Mice Inbred C57BL Wnt Proteins Endocrinology lcsh:Q Tomography X-Ray Computed |
| Zdroj: | PLoS ONE PLoS ONE, Vol 4, Iss 5, p e5438 (2009) PLoS ONE, 4 (5) |
| ISSN: | 1932-6203 |
| Popis: | We investigated the role of Lef1, one of the four transcription factors that transmit Wnt signaling to the genome, in the regulation of bone mass. Microcomputed tomographic analysis of 13- and 17-week-old mice revealed significantly reduced trabecular bone mass in Lef1+/− females compared to littermate wild-type females. This was attributable to decreased osteoblast activity and bone formation as indicated by histomorphometric analysis of bone remodeling. In contrast to females, bone mass was unaffected by Lef1 haploinsufficiency in males. Similarly, females were substantially more responsive than males to haploinsufficiency in Gsk3β, a negative regulator of the Wnt pathway, displaying in this case a high bone mass phenotype. Lef1 haploinsufficiency also led to low bone mass in males lacking functional androgen receptor (AR) (tfm mutants). The protective skeletal effect of AR against Wnt-related low bone mass is not necessarily a result of direct interaction between the AR and Wnt signaling pathways, because Lef1+/− female mice had normal bone mass at the age of 34 weeks. Thus, our results indicate an age- and gender-dependent role for Lef1 in regulating bone formation and bone mass in vivo. The resistance to Lef1 haploinsufficiency in males with active AR and in old females could be due to the reduced bone turnover in these mice. PLoS ONE, 4 (5) ISSN:1932-6203 |
| Databáze: | OpenAIRE |
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