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Altered Collagen in Tartrate-Resistant Acid Phosphatase (TRAP)-Deficient Mice: A Role for TRAP in Bone Collagen Metabolism

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Abstract

Tartrate-resistant acid phosphatase (TRAP) is an iron-containing protein that is highly expressed by osteoclasts, macrophages, and dendritic cells. The enzyme is secreted by osteoclasts during bone resorption, and serum TRAP activity correlates with resorptive activity in disorders of bone metabolism. TRAP is essential for normal skeletal development. In knockout mice lacking TRAP, bone shape and modeling is altered with increased mineral density. Here, we report the effect of TRAP on the biochemical and biomechanical properties of collagen, the major protein constituting the bone matrix, using these mice. Femurs from TRAP-/- and wild-type mice were used in these studies. The biomechanical properties were investigated using a three-point bending technique. Collagen synthesis was determined by measuring cross-link content using high-performance liquid chromatography and amino acid analysis. Collagen degradation was determined by measuring matrix metalloproteinase-2 (MMP-2) activity. The rates of collagen synthesis and degradation were significantly greater in bones from TRAP-/- mice compared with wild type. At 8 weeks, there was an increase in the intermediate cross-links but no significant difference in animals aged 6 months. There was a significant increase in mature cross-links at both ages. A significant increase in MMP-2 production both pro and active was observed. A significant increase in ultimate stress and Young’s modulus of elasticity was needed to fracture the bones from mice deficient in TRAP. We conclude that both synthesis as well as degradation of collagen are increased when TRAP is absent in mice at 8 weeks and 6 months of age, showing that TRAP has an important role in the metabolism of collagen.

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Acknowledgement

We thank Professor Allen Bailey for critical review of the manuscript and Tracy Dewey for assisting with the preparation of the figures. This work was supported by a grant from The Wellcome Trust.

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Authors and Affiliations

  1. School of Clinical Veterinary Science, University of Bristol, Langford, BS40 5DU, UK

    Helen C. Roberts, Lynda Knott, Nicholas C. Avery & Alison R. Hayman

  2. Department of Medicine, University of Cambridge, Addenbrooke’s Hospital, Cambridge, CB2 2QQ, UK

    Timothy M. Cox

  3. School of Biosciences, Cardiff University, Cardiff, CF10 3US, UK

    Martin J. Evans

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  1. Helen C. Roberts
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Correspondence to Alison R. Hayman.

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Roberts, H.C., Knott, L., Avery, N.C. et al. Altered Collagen in Tartrate-Resistant Acid Phosphatase (TRAP)-Deficient Mice: A Role for TRAP in Bone Collagen Metabolism. Calcif Tissue Int 80, 400–410 (2007). https://doi.org/10.1007/s00223-007-9032-2

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  • DOI: https://doi.org/10.1007/s00223-007-9032-2

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