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

被引:163
作者
Pavalko, FM
Norvell, SM
Burr, DB
Turner, CH
Duncan, RL
Bidwell, JP
机构
[1] Indiana Univ, Sch Med, Dept Anat & Cell Biol, Indianapolis, IN 46202 USA
[2] Indiana Univ, Sch Med, Dept Cellular & Integrat Physiol, Indianapolis, IN 46202 USA
[3] Indiana Univ, Sch Med, Dept Orthoped Surg, Indianapolis, IN USA
关键词
adhesion complex; architectural transcription factors; connective membrane skeleton proteins; nuclear matrix; tissue matrix; stretch-activated channels;
D O I
10.1002/jcb.10284
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. (C) 2002 Wiley-Liss, Inc.
引用
收藏
页码:104 / 112
页数:9
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