Smurf1 Inhibits Mesenchymal Stem Cell Proliferation and Differentiation into Osteoblasts through JunB Degradation

Smurf1 Inhibits Mesenchymal Stem Cell Proliferation and Differentiation into Osteoblasts through JunB Degradation

Ubiquitin ligase Smurf1-deficient mice develop an increased-bone-mass phenotype in an age-dependent manner. It was reported that such a bone-mass increase is related to enhanced activities of differentiated osteoblasts. Although osteoblasts are of mesenchymal stem cell (MSC) origin and MSC prolifera...

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Main Authors: Zhao, Lan, Huang, Jian, Guo, Ruolin, Wang, Yi, Chen, Di, Xing, Lianping
Format: Online
Language:English
Published: Wiley Subscription Services, Inc., A Wiley Company 2010
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3153132/
id pubmed-3153132
recordtype oai_dc
spelling pubmed-31531322011-08-19 Smurf1 Inhibits Mesenchymal Stem Cell Proliferation and Differentiation into Osteoblasts through JunB Degradation Zhao, Lan Huang, Jian Guo, Ruolin Wang, Yi Chen, Di Xing, Lianping Original Article Ubiquitin ligase Smurf1-deficient mice develop an increased-bone-mass phenotype in an age-dependent manner. It was reported that such a bone-mass increase is related to enhanced activities of differentiated osteoblasts. Although osteoblasts are of mesenchymal stem cell (MSC) origin and MSC proliferation and differentiation can have significant impacts on bone formation, it remains largely unknown whether regulation of MSCs plays a role in the bone-mass increase of Smurf1-deficient mice. In this study we found that bone marrow mesenchymal progenitor cells from Smurf1−/− mice form significantly increased alkaline phosphatase–positive colonies, indicating roles of MSC proliferation and differentiation in bone-mass accrual of Smurf1−/− mice. Interestingly, Smurf1−/− cells have an elevated protein level of AP-1 transcription factor JunB. Biochemical experiments demonstrate that Smurf1 interacts with JunB through the PY motif and targets JunB protein for ubiquitination and proteasomal degradation. Indeed, Smurf1-deficient MSCs have higher proliferation rates, consistent with the facts that cyclin D1 mRNA and protein both are increased in Smurf1−/− cells and JunB can induce cyclinD1 promoter. Moreover, JunB overexpression induces osteoblast differentiation, shown by higher expression of osteoblast markers, and JunB knock-down not only decreases osteoblast differentiation but also restores the osteogenic potential to wild-type level in Smurf1−/− cells. In conclusion, our results suggest that Smurf1 negatively regulates MSC proliferation and differentiation by controlling JunB turnover through an ubiquitin-proteasome pathway. © 2010 American Society for Bone and Mineral Research. Wiley Subscription Services, Inc., A Wiley Company 2010-06 2010-01-15 /pmc/articles/PMC3153132/ /pubmed/20200942 http://dx.doi.org/10.1002/jbmr.28 Text en Copyright © 2010 American Society for Bone and Mineral Research http://creativecommons.org/licenses/by/2.5/ Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Zhao, Lan
Huang, Jian
Guo, Ruolin
Wang, Yi
Chen, Di
Xing, Lianping
spellingShingle Zhao, Lan
Huang, Jian
Guo, Ruolin
Wang, Yi
Chen, Di
Xing, Lianping
Smurf1 Inhibits Mesenchymal Stem Cell Proliferation and Differentiation into Osteoblasts through JunB Degradation
author_facet Zhao, Lan
Huang, Jian
Guo, Ruolin
Wang, Yi
Chen, Di
Xing, Lianping
author_sort Zhao, Lan
title Smurf1 Inhibits Mesenchymal Stem Cell Proliferation and Differentiation into Osteoblasts through JunB Degradation
title_short Smurf1 Inhibits Mesenchymal Stem Cell Proliferation and Differentiation into Osteoblasts through JunB Degradation
title_full Smurf1 Inhibits Mesenchymal Stem Cell Proliferation and Differentiation into Osteoblasts through JunB Degradation
title_fullStr Smurf1 Inhibits Mesenchymal Stem Cell Proliferation and Differentiation into Osteoblasts through JunB Degradation
title_full_unstemmed Smurf1 Inhibits Mesenchymal Stem Cell Proliferation and Differentiation into Osteoblasts through JunB Degradation
title_sort smurf1 inhibits mesenchymal stem cell proliferation and differentiation into osteoblasts through junb degradation
description Ubiquitin ligase Smurf1-deficient mice develop an increased-bone-mass phenotype in an age-dependent manner. It was reported that such a bone-mass increase is related to enhanced activities of differentiated osteoblasts. Although osteoblasts are of mesenchymal stem cell (MSC) origin and MSC proliferation and differentiation can have significant impacts on bone formation, it remains largely unknown whether regulation of MSCs plays a role in the bone-mass increase of Smurf1-deficient mice. In this study we found that bone marrow mesenchymal progenitor cells from Smurf1−/− mice form significantly increased alkaline phosphatase–positive colonies, indicating roles of MSC proliferation and differentiation in bone-mass accrual of Smurf1−/− mice. Interestingly, Smurf1−/− cells have an elevated protein level of AP-1 transcription factor JunB. Biochemical experiments demonstrate that Smurf1 interacts with JunB through the PY motif and targets JunB protein for ubiquitination and proteasomal degradation. Indeed, Smurf1-deficient MSCs have higher proliferation rates, consistent with the facts that cyclin D1 mRNA and protein both are increased in Smurf1−/− cells and JunB can induce cyclinD1 promoter. Moreover, JunB overexpression induces osteoblast differentiation, shown by higher expression of osteoblast markers, and JunB knock-down not only decreases osteoblast differentiation but also restores the osteogenic potential to wild-type level in Smurf1−/− cells. In conclusion, our results suggest that Smurf1 negatively regulates MSC proliferation and differentiation by controlling JunB turnover through an ubiquitin-proteasome pathway. © 2010 American Society for Bone and Mineral Research.
publisher Wiley Subscription Services, Inc., A Wiley Company
publishDate 2010
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3153132/
_version_ 1611470003416072192

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