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A Model for mechanotransduction in bone cells: The load-bearing mechanosomes

Authors

  • Fred M. Pavalko,

    1. Department of Cellular and Integrative Physiology, Indiana University School of Medicine (IUSM), Indianapolis, Indiana
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  • Suzanne M. Norvell,

    1. Department of Cellular and Integrative Physiology, Indiana University School of Medicine (IUSM), Indianapolis, Indiana
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  • David B. Burr,

    1. Department of Anatomy and Cell Biology, Indiana University School of Medicine (IUSM), Indianapolis, Indiana
    2. Department of Orthopedic Surgery, Indiana University School of Medicine (IUSM), Indianapolis, Indiana
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  • Charles H. Turner,

    1. Department of Orthopedic Surgery, Indiana University School of Medicine (IUSM), Indianapolis, Indiana
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  • Randall L. Duncan,

    1. Department of Cellular and Integrative Physiology, Indiana University School of Medicine (IUSM), Indianapolis, Indiana
    2. Department of Orthopedic Surgery, Indiana University School of Medicine (IUSM), Indianapolis, Indiana
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  • Joseph P. Bidwell

    Corresponding author
    1. Department of Anatomy and Cell Biology, Indiana University School of Medicine (IUSM), Indianapolis, Indiana
    • Department of Anatomy and Cell Biology, Indiana University School of Medicine, Medical Science Bldg 5035, 635 Barnhill Drive, Indianapolis, IN 46202.
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Abstract

The skeleton's response to mechanical force, or load, has significance to space travel, the treatment of osteoporosis, and orthodontic appliances. How bone senses and processes load remains largely unknown. The cellular basis of mechanotransduction, however, likely involves the integration of diffusion-controlled signaling pathways with a solid-state scaffold linking the cell membrane to the genes. Here, we integrate various concepts from models of connective membrane skeleton proteins, cellular tensegrity, and nuclear matrix architectural transcription factors, to describe how a load-induced deformation of bone activates a change in the skeletal genetic program. We propose that mechanical information is relayed from the bone to the gene in part by a succession of deformations, changes in conformations, and translocations. The load-induced deformation of bone is converted into the deformation of the sensor cell membrane. This, in turn, drives conformational changes in membrane proteins of which some are linked to a solid-state signaling scaffold that releases protein complexes capable of carrying mechanical information, “mechanosomes”, into the nucleus. These mechanosomes translate this information into changes in the geometry of the 5′ regulatory region of target gene DNA altering gene activity; bending bone ultimately bends genes. We identify specific candidate proteins fitting the profile of load-signaling mechanosomes. © 2002 Wiley-Liss, Inc.

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