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High bone mass in the STR/ort mouse results from increased bone formation and impaired bone resorption and is associated with extramedullary hematopoiesis

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Abstract

We here describe the novel high bone mass phenotype in STR/ort mice that leads to increased bone masses of cortical and trabecular bone and is associated with elevated osteoblast activity and impaired osteoclast function alike. Comparison of STR/ort and C57BL/6 mice reveals an increase in trabecular bone volumes of the vertebrae and at femoral metaphysis. In the females, this difference is significant as early as 2 months of age and at 9 months the females by far exceed their age matched males in all parameters measured. The increase in cortical bone mass at femoral diaphysis results from an apposition to the endosteal surface, it is significant for both sexes as early as 1 month of age and leads to bone marrow compression and extramedullary hematopoiesis. Altered activities of both, the osteoblast and the osteoclast contribute to the high bone mass and collectively this phenotype supports a multifactorial pathogenesis. Moreover, the spontaneous development of osteoarthritis in male STR/ort mice is suggestive of a tight correlation between trabecular bone mass and the development of degenerative changes of the articular cartilage.

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Acknowledgments

This work was supported by grants from the German Research Foundation (DFG, MU 844/12-1) and the University of Rostock (FORUN). The authors would like to thank Marlies Dettmer (Institute of Immunology), Dorothea Frenz and Ilona Klamfuß (both of the Institute of Experimental Surgery) for expert technical assistance and Karin Gerber (Institute of Experimental Surgery) for taking excellent care of the animals. Special thanks go to Philipp Herlyn and Dagmar-Christiane Fischer for their support with the X-ray micro-computed tomography and to Bettina Willie for her help with the TRAcP stainings. We are also grateful for fruitful discussions with Brigitte Vollmar.

Conflict of interest

All authors have no conflicts of interest.

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Authors and Affiliations

  1. Institute of Immunology, University of Rostock, Schillingallee 68, 18057, Rostock, Germany

    Juliane Pasold, Robby Engelmann, Sarah Joost & Brigitte Müller-Hilke

  2. Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany

    Johannes Keller & Robert P. Marshall

  3. Department of Oral and Maxillofacial Plastic Surgery, University of Rostock, 18057, Rostock, Germany

    Bernhard Frerich

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  1. Juliane Pasold
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Correspondence to Brigitte Müller-Hilke.

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Pasold, J., Engelmann, R., Keller, J. et al. High bone mass in the STR/ort mouse results from increased bone formation and impaired bone resorption and is associated with extramedullary hematopoiesis. J Bone Miner Metab 31, 71–81 (2013). https://doi.org/10.1007/s00774-012-0394-9

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  • DOI: https://doi.org/10.1007/s00774-012-0394-9

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