Molecular regulation of mechanotransduction.
There is a common mechanism for mechanotransduction in cells, regardless of the cell type. Integrins, interacting with their matrix/environment, mediate increases in intracellular Ca2+ levels and activate MAP kinase cascades to cause ERK1/2 phosphorylation. Phosphorylated ERK1/2 causes the activation of the AP-1 family of transcription factors that are necessary for the pro-growth response. The pro-bone growth response involves upregulation of the genes c-fos, IGF-1, cyclooxygenase, and osteocalcin. In osteocytes, increases in intracellular Ca2+ levels may additionally occur by extracellular Ca2+ influx through a stretch-activated ion channel. Each bone cell appears fine-tuned for the type of stimulus, with accessory mechanotransduction signaling pathways, such as calcineurin-mediated activation of the tissue-specific transcription factor NF-AT, adjusting the outcome of signaling in each case.
Iqbal
Jameel
J
Mount Sinai Bone Program, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA. jameel.iqbal@mssm.edu
Zaidi
Mone
M
D000818:Animals; D001846:Bone Development / Q000502:physiology*; D001857:Bone Matrix / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology*; D016207:Cytokines / Q000502:physiology*; D005109:Extracellular Matrix / Q000502:physiology; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D010011:Osteocytes / Q000502:physiology*
D016207:Cytokines; D016023:Integrins