Beta-Catenin Haplo Insufficient Male Mice Do Not Lose Bone in Response to Hindlimb Unloading.
As the β-catenin pathway has been shown to be involved in mechanotransduction, we sought to determine if haploinsufficiency would affect skeletal response to unloading. It has previously been shown that deletion of both alleles of β-catenin in bone cells results in a fragile skeleton highly suscepti...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2016-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4943721?pdf=render |
| _version_ | 1818982658245394432 |
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| author | Delphine B Maurel Peipei Duan Joshua Farr An-Lin Cheng Mark L Johnson Lynda F Bonewald |
| author_facet | Delphine B Maurel Peipei Duan Joshua Farr An-Lin Cheng Mark L Johnson Lynda F Bonewald |
| author_sort | Delphine B Maurel |
| collection | DOAJ |
| description | As the β-catenin pathway has been shown to be involved in mechanotransduction, we sought to determine if haploinsufficiency would affect skeletal response to unloading. It has previously been shown that deletion of both alleles of β-catenin in bone cells results in a fragile skeleton highly susceptible to fracture, but deletion of one allele using Dmp1-Cre (Ctnnb1+/loxP; Dmp1-Cre, cKO HET) has little effect on the 2 mo old skeleton. We found that under normal housing conditions, trabecular bone volume was significantly less in 5 mo old male cKO HET mice compared to controls (Ctrl/HET:Tb. BV/TV = 13.96±2.71/8.92±0.95%, Tb.N. = 4.88±0.51/3.95±0.44/mm, Tb. Sp. = 0.20±0.02/0.26±0.03mm, a 36%, 19% and 30% change respectively) but not in females suggesting an age and gender related effect. Before performing suspension experiments and to control for the environmental effects, animals with the same tail attachment and housing conditions, but not suspended (NS), were compared to normally housed (NH) animals. Attachment and housing resulted in weight loss in both genders and phenotypes. Cortical bone loss was observed in the cKO HET males (NH/NS, Ct BV/TV: 90.45±0.72/89.12±0.56%) and both diaphyseal (0.19±0.01/0.17±0.01mm) and metaphyseal (0.10±0.01/0.08±0.01mm) thickness, but not in female cKO HET mice suggesting that male cKO HET mice are susceptible to attachment and housing conditions. These results with transgenic mice emphasizes the importance of proper controls when attributing skeletal responses to unloading. With suspension, cKO HET male mice did not lose bone unlike female cKO HET mice that had greater trabecular bone loss than controls (Ctrl 9%:cKO HET 21% decrease Tb. N; Ctrl 12%:cKO HET 27% increase Tb. Sp.). Suspended and non-suspended mice lost weight compared to normally housed animals. Taken together, the data suggest a protective effect of β-catenin against the effects of stress in males and partial protection against unloading in females. |
| first_indexed | 2024-12-20T17:50:43Z |
| format | Article |
| id | doaj.art-652763dd9a7e434a9be2297a52e4b7b1 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T17:50:43Z |
| publishDate | 2016-01-01 |
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| spelling | doaj.art-652763dd9a7e434a9be2297a52e4b7b12022-12-21T19:30:52ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01117e015838110.1371/journal.pone.0158381Beta-Catenin Haplo Insufficient Male Mice Do Not Lose Bone in Response to Hindlimb Unloading.Delphine B MaurelPeipei DuanJoshua FarrAn-Lin ChengMark L JohnsonLynda F BonewaldAs the β-catenin pathway has been shown to be involved in mechanotransduction, we sought to determine if haploinsufficiency would affect skeletal response to unloading. It has previously been shown that deletion of both alleles of β-catenin in bone cells results in a fragile skeleton highly susceptible to fracture, but deletion of one allele using Dmp1-Cre (Ctnnb1+/loxP; Dmp1-Cre, cKO HET) has little effect on the 2 mo old skeleton. We found that under normal housing conditions, trabecular bone volume was significantly less in 5 mo old male cKO HET mice compared to controls (Ctrl/HET:Tb. BV/TV = 13.96±2.71/8.92±0.95%, Tb.N. = 4.88±0.51/3.95±0.44/mm, Tb. Sp. = 0.20±0.02/0.26±0.03mm, a 36%, 19% and 30% change respectively) but not in females suggesting an age and gender related effect. Before performing suspension experiments and to control for the environmental effects, animals with the same tail attachment and housing conditions, but not suspended (NS), were compared to normally housed (NH) animals. Attachment and housing resulted in weight loss in both genders and phenotypes. Cortical bone loss was observed in the cKO HET males (NH/NS, Ct BV/TV: 90.45±0.72/89.12±0.56%) and both diaphyseal (0.19±0.01/0.17±0.01mm) and metaphyseal (0.10±0.01/0.08±0.01mm) thickness, but not in female cKO HET mice suggesting that male cKO HET mice are susceptible to attachment and housing conditions. These results with transgenic mice emphasizes the importance of proper controls when attributing skeletal responses to unloading. With suspension, cKO HET male mice did not lose bone unlike female cKO HET mice that had greater trabecular bone loss than controls (Ctrl 9%:cKO HET 21% decrease Tb. N; Ctrl 12%:cKO HET 27% increase Tb. Sp.). Suspended and non-suspended mice lost weight compared to normally housed animals. Taken together, the data suggest a protective effect of β-catenin against the effects of stress in males and partial protection against unloading in females.http://europepmc.org/articles/PMC4943721?pdf=render |
| spellingShingle | Delphine B Maurel Peipei Duan Joshua Farr An-Lin Cheng Mark L Johnson Lynda F Bonewald Beta-Catenin Haplo Insufficient Male Mice Do Not Lose Bone in Response to Hindlimb Unloading. PLoS ONE |
| title | Beta-Catenin Haplo Insufficient Male Mice Do Not Lose Bone in Response to Hindlimb Unloading. |
| title_full | Beta-Catenin Haplo Insufficient Male Mice Do Not Lose Bone in Response to Hindlimb Unloading. |
| title_fullStr | Beta-Catenin Haplo Insufficient Male Mice Do Not Lose Bone in Response to Hindlimb Unloading. |
| title_full_unstemmed | Beta-Catenin Haplo Insufficient Male Mice Do Not Lose Bone in Response to Hindlimb Unloading. |
| title_short | Beta-Catenin Haplo Insufficient Male Mice Do Not Lose Bone in Response to Hindlimb Unloading. |
| title_sort | beta catenin haplo insufficient male mice do not lose bone in response to hindlimb unloading |
| url | http://europepmc.org/articles/PMC4943721?pdf=render |
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