MCB
Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hankenson, K. D.
Right arrow Articles by Bornstein, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hankenson, K. D.
Right arrow Articles by Bornstein, P.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, July 2005, p. 5599-5606, Vol. 25, No. 13
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.13.5599-5606.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Mice with a Disruption of the Thrombospondin 3 Gene Differ in Geometric and Biomechanical Properties of Bone and Have Accelerated Development of the Femoral Head

Kurt D. Hankenson,1,{dagger} Sheriar G. Hormuzdi,2,{dagger},{ddagger} Jeffrey A. Meganck,3 and Paul Bornstein2,4*

Departments of Orthopaedic Surgery, and Cell and Developmental Biology and Unit for Laboratory Animal Medicine,1 Mechanical Engineering, University of Michigan, Ann Arbor, Michigan 48109,3 Departments of Biochemistry,2 Medicine, University of Washington, Seattle, Washington 981954

Received 6 January 2005/ Returned for modification 4 March 2005/ Accepted 27 March 2005

Thrombospondin 3 (TSP3) is structurally similar to cartilage oligomeric matrix protein (COMP/TSP5), but its function is unknown. To determine the functional significance of TSP3, we generated mice with a targeted disruption of Thbs3. TSP3-null mice are viable and fertile and show normal prenatal skeletal patterning, based on Alcian blue/Alizarin red S staining. However, subtle and transient abnormalities were detected in the developing postnatal skeleton. Young adult TSP3-null mice are heavier than controls, and analyses of the geometric and biomechanical properties of long bones show increases in the moments of inertia, endocortical and periostal radii, and failure load. The bones of 9-week-old TSP3-null male mice also have a significantly greater cortical area. Most of these differences were no longer detected in 15-week-old mice. Microcomputed tomography scans showed that the trabecular bone proximal to the femoral head growth plate developed at an earlier time in TSP3-null mice than in wild-type mice. Thus, vascular invasion and ossification start in the femoral heads of TSP3-null mice at 9 weeks, whereas the wild-type femoral head is still composed of hypertrophic chondroctyes in a calcified matrix at 15 weeks. These results provide evidence for a role for TSP3 in the regulation of skeletal maturation in mice.

* Corresponding author. Mailing address: Department of Biochemistry, Box 357350, University of Washington, Seattle, WA 98195. Phone: 206-543-1789. Fax: 206-685-4426. E-mail:bornsten{at}u.washington.edu.

{dagger} These two authors contributed equally.

{ddagger} Present address: University Hospital of Neurology, Heidelberg, Germany.

Molecular and Cellular Biology, July 2005, p. 5599-5606, Vol. 25, No. 13
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.13.5599-5606.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:



Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
J. Bacteriol. J. Virol. Eukaryot. Cell
Microbiol. Mol. Biol. Rev. Clin. Vaccine Immunol. All ASM Journals

Copyright © 2005 by the American Society for Microbiology. All rights reserved.