Differential aging of growth plate cartilage underlies differences in bone length and thus helps determine skeletal proportions.
Bones at different anatomical locations vary dramatically in size. For example, human femurs are 20-fold longer than the phalanges in the fingers and toes. The mechanisms responsible for these size differences are poorly understood. Bone elongation occurs at the growth plates and advances rapidly in...
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| Language: | English |
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Public Library of Science (PLoS)
2018-07-01
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| Series: | PLoS Biology |
| Online Access: | https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.2005263&type=printable |
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| author | Julian C Lui Youn Hee Jee Presley Garrison James R Iben Shanna Yue Michal Ad Quang Nguyen Bijal Kikani Yoshiyuki Wakabayashi Jeffrey Baron |
| author_facet | Julian C Lui Youn Hee Jee Presley Garrison James R Iben Shanna Yue Michal Ad Quang Nguyen Bijal Kikani Yoshiyuki Wakabayashi Jeffrey Baron |
| author_sort | Julian C Lui |
| collection | DOAJ |
| description | Bones at different anatomical locations vary dramatically in size. For example, human femurs are 20-fold longer than the phalanges in the fingers and toes. The mechanisms responsible for these size differences are poorly understood. Bone elongation occurs at the growth plates and advances rapidly in early life but then progressively slows due to a developmental program termed "growth plate senescence." This developmental program includes declines in cell proliferation and hypertrophy, depletion of cells in all growth plate zones, and extensive underlying changes in the expression of growth-regulating genes. Here, we show evidence that these functional, structural, and molecular senescent changes occur earlier in the growth plates of smaller bones (metacarpals, phalanges) than in the growth plates of larger bones (femurs, tibias) and that this differential aging contributes to the disparities in bone length. We also show evidence that the molecular mechanisms that underlie the differential aging between different bones involve modulation of critical paracrine regulatory pathways, including insulin-like growth factor (Igf), bone morphogenetic protein (Bmp), and Wingless and Int-1 (Wnt) signaling. Taken together, the findings reveal that the striking disparities in the lengths of different bones, which characterize normal mammalian skeletal proportions, is achieved in part by modulating the progression of growth plate senescence. |
| format | Article |
| id | doaj-art-5c6aa04e995a44a1aedfff68841de73b |
| institution | DOAJ |
| issn | 1544-9173 1545-7885 |
| language | English |
| publishDate | 2018-07-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj-art-5c6aa04e995a44a1aedfff68841de73b2025-08-20T02:54:49ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852018-07-01167e200526310.1371/journal.pbio.2005263Differential aging of growth plate cartilage underlies differences in bone length and thus helps determine skeletal proportions.Julian C LuiYoun Hee JeePresley GarrisonJames R IbenShanna YueMichal AdQuang NguyenBijal KikaniYoshiyuki WakabayashiJeffrey BaronBones at different anatomical locations vary dramatically in size. For example, human femurs are 20-fold longer than the phalanges in the fingers and toes. The mechanisms responsible for these size differences are poorly understood. Bone elongation occurs at the growth plates and advances rapidly in early life but then progressively slows due to a developmental program termed "growth plate senescence." This developmental program includes declines in cell proliferation and hypertrophy, depletion of cells in all growth plate zones, and extensive underlying changes in the expression of growth-regulating genes. Here, we show evidence that these functional, structural, and molecular senescent changes occur earlier in the growth plates of smaller bones (metacarpals, phalanges) than in the growth plates of larger bones (femurs, tibias) and that this differential aging contributes to the disparities in bone length. We also show evidence that the molecular mechanisms that underlie the differential aging between different bones involve modulation of critical paracrine regulatory pathways, including insulin-like growth factor (Igf), bone morphogenetic protein (Bmp), and Wingless and Int-1 (Wnt) signaling. Taken together, the findings reveal that the striking disparities in the lengths of different bones, which characterize normal mammalian skeletal proportions, is achieved in part by modulating the progression of growth plate senescence.https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.2005263&type=printable |
| spellingShingle | Julian C Lui Youn Hee Jee Presley Garrison James R Iben Shanna Yue Michal Ad Quang Nguyen Bijal Kikani Yoshiyuki Wakabayashi Jeffrey Baron Differential aging of growth plate cartilage underlies differences in bone length and thus helps determine skeletal proportions. PLoS Biology |
| title | Differential aging of growth plate cartilage underlies differences in bone length and thus helps determine skeletal proportions. |
| title_full | Differential aging of growth plate cartilage underlies differences in bone length and thus helps determine skeletal proportions. |
| title_fullStr | Differential aging of growth plate cartilage underlies differences in bone length and thus helps determine skeletal proportions. |
| title_full_unstemmed | Differential aging of growth plate cartilage underlies differences in bone length and thus helps determine skeletal proportions. |
| title_short | Differential aging of growth plate cartilage underlies differences in bone length and thus helps determine skeletal proportions. |
| title_sort | differential aging of growth plate cartilage underlies differences in bone length and thus helps determine skeletal proportions |
| url | https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.2005263&type=printable |
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