Document Detail

Overexpression of H1 calponin in osteoblast lineage cells leads to a decrease in bone mass by disrupting osteoblast function and promoting osteoclast formation.
MedLine Citation:
PMID:  23044709     Owner:  NLM     Status:  MEDLINE    
H1 calponin (CNN1) is known as a smooth muscle-specific, actin-binding protein which regulates smooth muscle contractive activity. Although previous studies have shown that CNN1 has effect on bone, the mechanism is not well defined. To investigate the role of CNN1 in maintaining bone homeostasis, we generated transgenic mice overexpressing Cnn1 under the control of the osteoblast-specific 3.6-kb Col1a1 promoter. Col1a1-Cnn1 transgenic mice showed delayed bone formation at embryonic stage and decreased bone mass at adult stage. Morphology analyses showed reduced trabecular number, thickness and defects in bone formation. The proliferation and migration of osteoblasts were decreased in Col1a1-Cnn1 mice due to alterations in cytoskeleton. The early osteoblast differentiation of Col1a1-Cnn1 mice was increased, but the late stage differentiation and mineralization of osteoblasts derived from Col1a1-Cnn1 mice were significantly decreased. In addition to impaired bone formation, the decreased bone mass was also associated with enhanced osteoclastogenesis. Tartrate-resistant acid phosphatase (TRAP) staining revealed increased osteoclast numbers in tibias of 2-month-old Col1a1-Cnn1 mice, and increased numbers of osteoclasts co-cultured with Col1a1-Cnn1 osteoblasts. The ratio of RANKL to OPG was significantly increased in Col1a1-Cnn1 osteoblasts. These findings reveal a novel function of CNN1 in maintaining bone homeostasis by coupling bone formation to bone resorption.
Nan Su; Maomao Chen; Siyu Chen; Can Li; Yangli Xie; Ying Zhu; Yaozong Zhang; Ling Zhao; Qifen He; Xiaolan Du; Di Chen; Lin Chen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research     Volume:  28     ISSN:  1523-4681     ISO Abbreviation:  J. Bone Miner. Res.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-18     Completed Date:  2013-08-29     Revised Date:  2014-07-14    
Medline Journal Info:
Nlm Unique ID:  8610640     Medline TA:  J Bone Miner Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  660-71     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 American Society for Bone and Mineral Research.
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MeSH Terms
Base Sequence
Biomechanical Phenomena
Bone Development
Calcium-Binding Proteins / genetics,  metabolism*
Cell Differentiation
Cell Lineage
Cell Proliferation
Coculture Techniques
Collagen Type I / genetics
DNA Primers
Mice, Transgenic
Microfilament Proteins / genetics,  metabolism*
Osteoblasts / cytology,  metabolism*
Osteoporosis / metabolism*
Promoter Regions, Genetic
Real-Time Polymerase Chain Reaction
Grant Support
Reg. No./Substance:
0/Calcium-Binding Proteins; 0/Collagen Type I; 0/DNA Primers; 0/Microfilament Proteins; 0/calponin; 0/collagen type I, alpha 1 chain

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