BMP-9-induced muscle heterotopic ossification requires changes to the skeletal muscle microenvironment

Authors

  • Elisabeth Leblanc,

    1. Research Centre on Ageing, Sherbrooke, Quebec, Canada
    2. Department of Orthopedic Surgery, Faculty of Medicine, Université de Sherbrooke, Sherbrooke, Quebec, Canada
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  • Frédéric Trensz,

    1. Research Centre on Ageing, Sherbrooke, Quebec, Canada
    2. Department of Orthopedic Surgery, Faculty of Medicine, Université de Sherbrooke, Sherbrooke, Quebec, Canada
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  • Sonia Haroun,

    1. Research Centre on Ageing, Sherbrooke, Quebec, Canada
    2. Department of Orthopedic Surgery, Faculty of Medicine, Université de Sherbrooke, Sherbrooke, Quebec, Canada
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  • Geneviève Drouin,

    1. Research Centre on Ageing, Sherbrooke, Quebec, Canada
    2. Department of Orthopedic Surgery, Faculty of Medicine, Université de Sherbrooke, Sherbrooke, Quebec, Canada
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  • Éric Bergeron,

    1. Department of Chemical and Biotechnological Engineering, Faculty of Engineering, Université de Sherbrooke, Sherbrooke, Quebec, Canada
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  • Christopher M Penton,

    1. Center for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA
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  • Federica Montanaro,

    1. Center for Gene Therapy, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA
    2. Department of Physiology and Cell Biology and Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, USA
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  • Sophie Roux,

    1. Étienne-Lebel Clinical Research Centre, Sherbrooke, Quebec, Canada
    2. Department of Medicine, Faculty of Medicine, Université de Sherbrooke, Sherbrooke, Quebec, Canada
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  • Nathalie Faucheux,

    1. Étienne-Lebel Clinical Research Centre, Sherbrooke, Quebec, Canada
    2. Department of Chemical and Biotechnological Engineering, Faculty of Engineering, Université de Sherbrooke, Sherbrooke, Quebec, Canada
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  • Guillaume Grenier

    Corresponding author
    1. Research Centre on Ageing, Sherbrooke, Quebec, Canada
    2. Étienne-Lebel Clinical Research Centre, Sherbrooke, Quebec, Canada
    3. Department of Orthopedic Surgery, Faculty of Medicine, Université de Sherbrooke, Sherbrooke, Quebec, Canada
    • Department of Orthopedic Surgery, Faculty of Medicine, Université de Sherbrooke, 3001 12th Avenue North, Sherbrooke, Quebec, J1H 5N4, Canada.
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  • For a Commentary on this article, please see Shore (J Bone Miner Res. 2011;26:1163-1165. DOI: 10.1002/jbmr.404) .

Abstract

Heterotopic ossification (HO) is defined as the formation of bone inside soft tissue. Symptoms include joint stiffness, swelling, and pain. Apart from the inherited form, the common traumatic form generally occurs at sites of injury in damaged muscles and is often associated with brain injury. We investigated bone morphogenetic protein 9 (BMP-9), which possesses a strong osteoinductive capacity, for its involvement in muscle HO physiopathology. We found that BMP-9 had an osteoinductive influence on mouse muscle resident stromal cells by increasing their alkaline phosphatase activity and bone-specific marker expression. Interestingly, BMP-9 induced HO only in damaged muscle, whereas BMP-2 promoted HO in skeletal muscle regardless of its state. The addition of the soluble form of the ALK1 protein (the BMP-9 receptor) significantly inhibited the osteoinductive potential of BMP-9 in cells and HO in damaged muscles. BMP-9 thus should be considered a candidate for involvement in HO physiopathology, with its activity depending on the skeletal muscle microenvironment. © 2011 American Society for Bone and Mineral Research.

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