Overexpression of TIMP-3 in Chondrocytes Produces Transient Reduction in Growth Plate Length but Permanently Reduces Adult Bone Quality and Quantity.
Bone development and length relies on the growth plate formation, which is dependent on degradative enzymes such as MMPs. Indeed, deletion of specific members of this enzyme family in mice results in important joint and bone abnormalities, suggesting a role in skeletal development. As such, the cont...
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doaj-d8a31e29409543a5b3d8ddd154c062ff2021-03-04T12:37:53ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-011112e016797110.1371/journal.pone.0167971Overexpression of TIMP-3 in Chondrocytes Produces Transient Reduction in Growth Plate Length but Permanently Reduces Adult Bone Quality and Quantity.Blandine PouletKe LiuDarren PlumbPhoung VoMittal ShahKatherine StainesAlexandra SampsonHiroyuki NakamuraHideaki NagaseAlessandra CarrieroSandra ShefelbineAndrew A PitsillidesGeorge Bou-GhariosBone development and length relies on the growth plate formation, which is dependent on degradative enzymes such as MMPs. Indeed, deletion of specific members of this enzyme family in mice results in important joint and bone abnormalities, suggesting a role in skeletal development. As such, the control of MMP activity is vital in the complex process of bone formation and growth. We generated a transgenic mouse line to overexpress TIMP3 in mouse chondrocytes using the Col2a1-chondrocyte promoter. This overexpression in cartilage resulted in a transient shortening of growth plate in homozygote mice but bone length was restored at eight weeks of age. However, tibial bone structure and mechanical properties remained compromised. Despite no transgene expression in adult osteoblasts from transgenic mice in vitro, their differentiation capacity was decreased. Neonates, however, did show transgene expression in a subset of bone cells. Our data demonstrate for the first time that transgene function persists in the chondro-osseous lineage continuum and exert influence upon bone quantity and quality.https://doi.org/10.1371/journal.pone.0167971 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Blandine Poulet Ke Liu Darren Plumb Phoung Vo Mittal Shah Katherine Staines Alexandra Sampson Hiroyuki Nakamura Hideaki Nagase Alessandra Carriero Sandra Shefelbine Andrew A Pitsillides George Bou-Gharios |
spellingShingle |
Blandine Poulet Ke Liu Darren Plumb Phoung Vo Mittal Shah Katherine Staines Alexandra Sampson Hiroyuki Nakamura Hideaki Nagase Alessandra Carriero Sandra Shefelbine Andrew A Pitsillides George Bou-Gharios Overexpression of TIMP-3 in Chondrocytes Produces Transient Reduction in Growth Plate Length but Permanently Reduces Adult Bone Quality and Quantity. PLoS ONE |
author_facet |
Blandine Poulet Ke Liu Darren Plumb Phoung Vo Mittal Shah Katherine Staines Alexandra Sampson Hiroyuki Nakamura Hideaki Nagase Alessandra Carriero Sandra Shefelbine Andrew A Pitsillides George Bou-Gharios |
author_sort |
Blandine Poulet |
title |
Overexpression of TIMP-3 in Chondrocytes Produces Transient Reduction in Growth Plate Length but Permanently Reduces Adult Bone Quality and Quantity. |
title_short |
Overexpression of TIMP-3 in Chondrocytes Produces Transient Reduction in Growth Plate Length but Permanently Reduces Adult Bone Quality and Quantity. |
title_full |
Overexpression of TIMP-3 in Chondrocytes Produces Transient Reduction in Growth Plate Length but Permanently Reduces Adult Bone Quality and Quantity. |
title_fullStr |
Overexpression of TIMP-3 in Chondrocytes Produces Transient Reduction in Growth Plate Length but Permanently Reduces Adult Bone Quality and Quantity. |
title_full_unstemmed |
Overexpression of TIMP-3 in Chondrocytes Produces Transient Reduction in Growth Plate Length but Permanently Reduces Adult Bone Quality and Quantity. |
title_sort |
overexpression of timp-3 in chondrocytes produces transient reduction in growth plate length but permanently reduces adult bone quality and quantity. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2016-01-01 |
description |
Bone development and length relies on the growth plate formation, which is dependent on degradative enzymes such as MMPs. Indeed, deletion of specific members of this enzyme family in mice results in important joint and bone abnormalities, suggesting a role in skeletal development. As such, the control of MMP activity is vital in the complex process of bone formation and growth. We generated a transgenic mouse line to overexpress TIMP3 in mouse chondrocytes using the Col2a1-chondrocyte promoter. This overexpression in cartilage resulted in a transient shortening of growth plate in homozygote mice but bone length was restored at eight weeks of age. However, tibial bone structure and mechanical properties remained compromised. Despite no transgene expression in adult osteoblasts from transgenic mice in vitro, their differentiation capacity was decreased. Neonates, however, did show transgene expression in a subset of bone cells. Our data demonstrate for the first time that transgene function persists in the chondro-osseous lineage continuum and exert influence upon bone quantity and quality. |
url |
https://doi.org/10.1371/journal.pone.0167971 |
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