Journal of Bone and Mineral Metabolism

, Volume 30, Issue 3, pp 304–311 | Cite as

Over-expression of Adamts1 in mice alters bone mineral density

  • Lijuan Hu
  • Kenneth B. Jonsson
  • Harriet Andersén
  • Anne Edenro
  • Mohammad Bohlooly-Y
  • Håkan Melhus
  • Thomas Lind
Original Article
First Online:
Received:
Accepted:

Abstract

ADAMTS1, a secreted multifunctional metalloproteinase with disintegrin and thrombospondin motifs, is an early response gene of parathyroid hormone (PTH) in osteoblasts. Mice engineered to lack Adamts1 are smaller compared to wild-type (WT) mice and ADAMTS1 metalloproteinase activity has been shown to increase osteoblastic growth in collagen gels. However, there are no reports investigating the consequence of Adamts1 over-expression on bone tissue in vivo. Here, we analyze bones of female and male transgenic (TG) mice over-expressing mouse Adamts1 using peripheral quantitative computed tomography to evaluate its effect on bone shape and mineral density. Western blotting of protein extracts and immunohistochemistry of bone sections reveal increased presence of Adamts1 protein in TG bones compared to WT bones. Phenotypic analyses of femur show that female TG mice have reduced metaphyseal total density, trabecular bone mineral density and trabecular mineral content. In contrast, male TG mice which were without changes in the metaphysis showed increased total density and cortical density at the mid-diaphysis cortical site. Female TG mice showed no significant changes at the cortical site compared to WT mice. Furthermore, diaphyseal endosteal compartment was only affected in male TG mice. Along these lines, Adamts1 increased blood levels of PTH only in females whereas it reduced osteocalcin levels only in males. These results reveal that Adamts1 has an impact on bone mineral density and thus further confirm Adamts1 as a potent regulator of bone remodeling.

Keywords

Adamts1 Bone mineral density Mouse pQCT Transgenic 
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Notes

Acknowledgments

We acknowledge and thank additional ATCG members at AstraZeneca R&D that have been involved in producing this transgenic model. In addition, we would like to thank Peter Brodin for providing the mouse Adamts1 cDNA and Brittmarie Andersson for her invaluable help in the pQCT measurements. Funding was provided by LIONS Cancer Research Fund, Uppsala, Sweden. AstraZeneca, Mölndal Sweden.

Conflict of interest

Harriet Andersén, Anne Edenro and Mohammad Bohlooly-Y are employees of AstraZeneca. Lijuan Hu, Kenneth B. Jonsson, Håkan Melhus and Thomas Lind have no financial conflicts of interest. The authors state that they have full control of all primary data and that they agree to allow the journal to review their data if requested.

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Copyright information

© The Japanese Society for Bone and Mineral Research and Springer 2011

Authors and Affiliations

  • Lijuan Hu
    • 1
  • Kenneth B. Jonsson
    • 2
  • Harriet Andersén
    • 3
  • Anne Edenro
    • 3
  • Mohammad Bohlooly-Y
    • 3
  • Håkan Melhus
    • 1
  • Thomas Lind
    • 1
  1. 1.Department of Medical Sciences, Section of Clinical PharmacologyUniversity HospitalUppsalaSweden
  2. 2.Department of Surgical SciencesUppsala University HospitalUppsalaSweden
  3. 3.AstraZeneca Transgenics and Comparative Genomics (ATCG)AstraZeneca R&D MölndalMölndalSweden

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