RT Journal Article ID 79093c3333557c1a A1 Robling, Alexander G. A1 Turner, Charles H. T1 Mechanical Signaling for Bone Modeling and Remodeling JF Critical Reviews™ in Eukaryotic Gene Expression JO CRE YR 2009 FD 2009-10-08 VO 19 IS 4 SP 319 OP 338 K1 mechanical loading K1 bone mechanotransduction K1 bone strength K1 adaptation K1 osteoblasts K1 osteocytes K1 Wnt signaling K1 focal adhesion K1 bone turnover K1 bone modeling K1 nitric oxide K1 prostaglandin K1 desensitization AB Proper development of the skeleton in utero and during growth requires mechanical stimulation. Loading results in adaptive changes in bone that strengthen bone structure. Bone’s adaptive response is regulated by the ability of resident bone cells to perceive and translate mechanical energy into a cascade of structural and biochemical changes within the cells — a process known as mechanotransduction. Mechanotransduction pathways are among the most anabolic in bone, and consequently, there is great interest in elucidating how mechanical loading produces its observed effects, including increased bone formation, reduced bone loss, changes in bone cell differentiation and lifespan, among others. A molecular understanding of these processes is developing, and with it comes a profound new insight into the biology of bone. In this article, we review the nature of the physical stimulus to which bone cells mount an adaptive response, including the identity of the sensor cells, their attributes and physical environment, and putative mechanoreceptors they express. Particular attention is allotted to the focal adhesion and Wnt signaling, in light of their emerging role in bone mechanotransduction. Te cellular mechanisms for increased bone loss during disuse, and reduced bone loss during loading are considered. Finally, we summarize the published data on bone cell accommodation, whereby bone cells stop responding to mechanical signaling events. Collectively, these data highlight the complex yet finely orchestrated process of mechanically regulated bone homeostasis. PB Begell House LK https://www.dl.begellhouse.com/journals/6dbf508d3b17c437,3837c3e737b547ae,79093c3333557c1a.html