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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred


IMPACT FACTOR 2018: 3.014
5-year IMPACT FACTOR: 3.162

CiteScore 2018: 3.09

SCImago Journal Rank (SJR) 2018: 1.482
Source Normalized Impact per Paper (SNIP) 2018: 0.820

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1431-6730
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Volume 392, Issue 10

Issues

Lack of ADAM15 in mice is associated with increased osteoblast function and bone mass

Marilena Marzia
  • Endocrine Unit, Massachusetts General Hospital and Harvard University School of Medicine, Boston, MA 02115, USA
  • Department of Orthopedics and Rehabilitation, Yale University School of Medicine, New Haven, CT 06510, USA
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  • De Gruyter OnlineGoogle Scholar
/ Victor Guaiquil
  • Arthritis and Tissue Degeneration Program, Hospital for Special Surgery, Cornell University, New York, NY 10021, USA
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  • De Gruyter OnlineGoogle Scholar
/ William C. Horne
  • Department of Orthopedics and Rehabilitation, Yale University School of Medicine, New Haven, CT 06510, USA
  • Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA 02115, USA
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/ Carl P. Blobel
  • Arthritis and Tissue Degeneration Program, Hospital for Special Surgery, Cornell University, New York, NY 10021, USA
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  • De Gruyter OnlineGoogle Scholar
/ Roland Baron
  • Endocrine Unit, Massachusetts General Hospital and Harvard University School of Medicine, Boston, MA 02115, USA
  • Department of Orthopedics and Rehabilitation, Yale University School of Medicine, New Haven, CT 06510, USA
  • Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA 02115, USA
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  • De Gruyter OnlineGoogle Scholar
/ Riccardo Chiusaroli
  • Endocrine Unit, Massachusetts General Hospital and Harvard University School of Medicine, Boston, MA 02115, USA
  • Department of Orthopedics and Rehabilitation, Yale University School of Medicine, New Haven, CT 06510, USA
  • Preclinical Pharmacology, Pharmacology and Toxicology Department, Rottapharm R&D, I-20052 Monza, Italy
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Published Online: 2011-07-30 | DOI: https://doi.org/10.1515/BC.2011.080

Abstract

The ADAMs (a disintegrin and metalloprotease) contribute to various biological functions including the development of tissues by taking part in cell-cell and cell-matrix interactions. We previously found that ADAM15 is prominently expressed in osteoblasts and to a lesser extent in osteoclasts. The aim of this study was to investigate a possible function of ADAM15 in bone. Adult ADAM15-/- mice displayed an increase in bone volume and thickness with an increase in the number and activity of osteoblasts, whereas osteoclasts were apparently unaffected. We found an increase in proliferation, alkaline phosphatase (ALP) staining and nodule deposition, and mineralization in cultures of ADAM15-/- osteoblasts compared to wild-type osteoblasts. We also observed an increase in β-catenin immunoreactivity in the nucleus of ADAM15-/- osteoblasts compared to wild-type, whereas β-catenin in the membrane/cytoplasm compartment appeared to undergo increased degradation. Furthermore, cyclin D1 and c-Jun, known downstream targets of β-catenin and effectors of cell activation, were found up-regulated in absence of ADAM15. This study indicates that ADAM15 is required for normal skeletal homeostasis and that its absence causes increased nuclear translocation of β-catenin in osteoblasts leading to increased osteoblast proliferation and function, which results in higher trabecular and cortical bone mass.

Keywords: ADAM15; β-catenin; disintegrin; metalloprotease; osteoblast; skeletal homeostasis

About the article

Corresponding author


Received: 2011-03-17

Accepted: 2011-06-19

Published Online: 2011-07-30

Published in Print: 2011-10-01


Citation Information: Biological Chemistry, Volume 392, Issue 10, Pages 877–885, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/BC.2011.080.

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