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Disturbed Synthesis of Type II Collagen Interferes with Rate of Bone Formation and Growth and Increases Bone Resorption in Transgenic Mice

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Abstract

Transgenic mice carrying an internally deleted human type II collagen gene (COL2A1) were used to study bone growth and development. This mutation has previously been shown to disturb the development of collagen fibrils in articular cartilage, causing chondrodysplasia and osteoarthritis. Type II collagen expression in bones was investigated with immunohistochemistry. The development and mineralization of the skeleton and anthropometric measurements on bones were evaluated using X-rays and dynamic histomorphometry. Type II collagen was expressed in the cartilage of developing bones. The bones of transgenic mice were smaller compared with the controls. The bone mass remained almost unchanged in transgenic mice after 1 month of age, leading to differences of 47% in trabecular bone volume (P = 0.012) and 40% in trabecular thickness (P < 0.01) at the age of 3 months compared with controls. At the age of 3 months the eroded surface per bone volume was 31% greater in transgenic mice compared with controls (P < 0.05). Trabecular thickness correlated positively with body weight (R = 0.71, P < 0.001). Interestingly, body weight correlated with bone volume in control mice (R = 0.27, P < 0.01), but no correlation was observed in transgenic mice. The disturbed synthesis of cartilage-specific type II collagen in growing transgenic mice retarded bone development, increased bone resorption, and altered tissue properties. This led to a negative net bone balance and small bone size. The results support the idea that an altered synthesis of cartilage-specific molecule(s) can disturb postnatal bone development and growth.

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Acknowledgments

This study was supported by the Research Foundation of Orthopedics and Traumatology in Finland, the Academy of Finland, and the Ministry of Education in Finland.

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Authors and Affiliations

  1. Coxa Hospital for Joint Replacement, PO Box 652, FIN-33101, Tampere, Finland

    Jyrki Nieminen

  2. Department of Orthopedic Surgery, University Hospital of Kuopio, Kuopio, Finland

    Janne Sahlman

  3. Department of Anatomy, Institute of Biomedicine, University of Kuopio, Kuopio, Finland

    Teemu Hirvonen & Heikki J. Helminen

  4. National Agency for Medicines, Helsinki, Finland

    Tuomo Lapveteläinen

  5. Armed Forces Institute of Pathology, Washington, DC, USA

    Markku Miettinen

  6. Central Hospital of Kanta-Häme, Hämeenlinna, Finland

    Ilkka Arnala

  7. Bone Diagnostic and Research Center, University of Kentucky, Lexington, KY, USA

    Hartmut H. Malluche

Authors
  1. Jyrki Nieminen
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  2. Janne Sahlman
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  3. Teemu Hirvonen
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  4. Tuomo Lapveteläinen
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  5. Markku Miettinen
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  8. Heikki J. Helminen
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Correspondence to Jyrki Nieminen.

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Nieminen, J., Sahlman, J., Hirvonen, T. et al. Disturbed Synthesis of Type II Collagen Interferes with Rate of Bone Formation and Growth and Increases Bone Resorption in Transgenic Mice. Calcif Tissue Int 82, 229–237 (2008). https://doi.org/10.1007/s00223-008-9110-0

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  • DOI: https://doi.org/10.1007/s00223-008-9110-0

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