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

Fred M. Pavalko, Suzanne M. Norvell, David B. Burr, Charles H. Turner, Randall L. Duncan, Joseph P. Bidwell

Research output: Contribution to journalReview article

184 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)104-112
Number of pages9
JournalJournal of Cellular Biochemistry
Volume88
Issue number1
DOIs
StatePublished - Jan 1 2003

Keywords

  • Adhesion complex
  • Architectural transcription factors
  • Connective membrane skeleton proteins
  • Nuclear matrix
  • Stretch-activated channels
  • Tissue matrix

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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