Antagonistic interplay between mechanical forces and glucocorticoids in bone: a tale of kinases.
The contrasting actions of mechanical forces and glucocorticoids (GC) on bone have been long recognized. However, the cellular and molecular mechanisms by which these stimuli impact the skeleton remain only partially known. Recent evidence gained from studies on bone cell apoptosis has revealed that mechanical forces and GC exhibit converse effects on osteocyte and osteoblast survival resulting from divergent actions on the focal adhesion kinases FAK and Pyk2, molecules that regulate integrin-dependent interactions between bone cells and the extracellular matrix (ECM). This prospect reviews these findings and poses the possibility that similar opposing effects on kinase signaling are responsible for other actions of mechanical forces and GC on the skeleton, in particular on bone formation and the Wnt signaling pathway.
Bellido
Teresita
T
Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. tbellido@iupui.edu
D000818:Animals; D001842:Bone and Bones / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D051418:Focal Adhesion Kinase 2 / Q000378:metabolism; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D005938:Glucocorticoids / Q000378:metabolism*; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction; D013314:Stress, Mechanical; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
D005938:Glucocorticoids; D051153:Wnt Proteins; D051176:beta Catenin; D011505:Protein-Tyrosine Kinases; D051418:Focal Adhesion Kinase 2; D051416:Focal Adhesion Protein-Tyrosine Kinases