Lef1 haploinsufficient mice display a low turnover and low bone mass phenotype in a gender- and age-specific manner.
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 litte...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2009-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0005438&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849687112947859456 |
|---|---|
| author | Tommy Noh Yankel Gabet Jon Cogan Yunfan Shi Archana Tank Tomoyo Sasaki Braden Criswell Alexis Dixon Christopher Lee Joseph Tam Thomas Kohler Eran Segev Lisa Kockeritz James Woodgett Ralph Müller Yang Chai Elisheva Smith Itai Bab Baruch Frenkel |
| author_facet | Tommy Noh Yankel Gabet Jon Cogan Yunfan Shi Archana Tank Tomoyo Sasaki Braden Criswell Alexis Dixon Christopher Lee Joseph Tam Thomas Kohler Eran Segev Lisa Kockeritz James Woodgett Ralph Müller Yang Chai Elisheva Smith Itai Bab Baruch Frenkel |
| author_sort | Tommy Noh |
| collection | DOAJ |
| description | 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 Gsk3beta, 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. |
| format | Article |
| id | doaj-art-6eb67f210fce47ed908c41e79dd00a92 |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2009-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-6eb67f210fce47ed908c41e79dd00a922025-08-20T03:22:26ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-01-0145e543810.1371/journal.pone.0005438Lef1 haploinsufficient mice display a low turnover and low bone mass phenotype in a gender- and age-specific manner.Tommy NohYankel GabetJon CoganYunfan ShiArchana TankTomoyo SasakiBraden CriswellAlexis DixonChristopher LeeJoseph TamThomas KohlerEran SegevLisa KockeritzJames WoodgettRalph MüllerYang ChaiElisheva SmithItai BabBaruch FrenkelWe 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 Gsk3beta, 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0005438&type=printable |
| spellingShingle | Tommy Noh Yankel Gabet Jon Cogan Yunfan Shi Archana Tank Tomoyo Sasaki Braden Criswell Alexis Dixon Christopher Lee Joseph Tam Thomas Kohler Eran Segev Lisa Kockeritz James Woodgett Ralph Müller Yang Chai Elisheva Smith Itai Bab Baruch Frenkel Lef1 haploinsufficient mice display a low turnover and low bone mass phenotype in a gender- and age-specific manner. PLoS ONE |
| title | Lef1 haploinsufficient mice display a low turnover and low bone mass phenotype in a gender- and age-specific manner. |
| title_full | Lef1 haploinsufficient mice display a low turnover and low bone mass phenotype in a gender- and age-specific manner. |
| title_fullStr | Lef1 haploinsufficient mice display a low turnover and low bone mass phenotype in a gender- and age-specific manner. |
| title_full_unstemmed | Lef1 haploinsufficient mice display a low turnover and low bone mass phenotype in a gender- and age-specific manner. |
| title_short | Lef1 haploinsufficient mice display a low turnover and low bone mass phenotype in a gender- and age-specific manner. |
| title_sort | lef1 haploinsufficient mice display a low turnover and low bone mass phenotype in a gender and age specific manner |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0005438&type=printable |
| work_keys_str_mv | AT tommynoh lef1haploinsufficientmicedisplayalowturnoverandlowbonemassphenotypeinagenderandagespecificmanner AT yankelgabet lef1haploinsufficientmicedisplayalowturnoverandlowbonemassphenotypeinagenderandagespecificmanner AT joncogan lef1haploinsufficientmicedisplayalowturnoverandlowbonemassphenotypeinagenderandagespecificmanner AT yunfanshi lef1haploinsufficientmicedisplayalowturnoverandlowbonemassphenotypeinagenderandagespecificmanner AT archanatank lef1haploinsufficientmicedisplayalowturnoverandlowbonemassphenotypeinagenderandagespecificmanner AT tomoyosasaki lef1haploinsufficientmicedisplayalowturnoverandlowbonemassphenotypeinagenderandagespecificmanner AT bradencriswell lef1haploinsufficientmicedisplayalowturnoverandlowbonemassphenotypeinagenderandagespecificmanner AT alexisdixon lef1haploinsufficientmicedisplayalowturnoverandlowbonemassphenotypeinagenderandagespecificmanner AT christopherlee lef1haploinsufficientmicedisplayalowturnoverandlowbonemassphenotypeinagenderandagespecificmanner AT josephtam lef1haploinsufficientmicedisplayalowturnoverandlowbonemassphenotypeinagenderandagespecificmanner AT thomaskohler lef1haploinsufficientmicedisplayalowturnoverandlowbonemassphenotypeinagenderandagespecificmanner AT eransegev lef1haploinsufficientmicedisplayalowturnoverandlowbonemassphenotypeinagenderandagespecificmanner AT lisakockeritz lef1haploinsufficientmicedisplayalowturnoverandlowbonemassphenotypeinagenderandagespecificmanner AT jameswoodgett lef1haploinsufficientmicedisplayalowturnoverandlowbonemassphenotypeinagenderandagespecificmanner AT ralphmuller lef1haploinsufficientmicedisplayalowturnoverandlowbonemassphenotypeinagenderandagespecificmanner AT yangchai lef1haploinsufficientmicedisplayalowturnoverandlowbonemassphenotypeinagenderandagespecificmanner AT elishevasmith lef1haploinsufficientmicedisplayalowturnoverandlowbonemassphenotypeinagenderandagespecificmanner AT itaibab lef1haploinsufficientmicedisplayalowturnoverandlowbonemassphenotypeinagenderandagespecificmanner AT baruchfrenkel lef1haploinsufficientmicedisplayalowturnoverandlowbonemassphenotypeinagenderandagespecificmanner |