Cyclic tensile stretch inhibition of nitric oxide release from osteoblast-like cells is both G protein and actin-dependent

Recent reports indicate the alteration of nitric oxide (NO) synthesis with mechanical stress loaded on the osteoblast and NO is considered to have a s ignificant role in mechanotransduction. We found the involvement of guanine -nucleotide-binding regulatory proteins (G proteins), especially Gi, in str ess-inhibited NO release of osteoblast-like cells (JOR:17;593-597. 1999). T o determine further the mechanism involved in this process, we measured c-J un N-terminal kinase/stress-activated protein kinase (JNK/SAPK) activity un der cyclic tensile stretch loaded on osteoblast-like cells. Cyclic stretch significantly enhanced JNK/SAPK activity and pertussis toxin clearly revers ed stress-enhanced JNK/SAPK activity. Cytochalasin D, actin microfilament d isrupting reagent, also abolished the stress activation of JNK/SAPK. We pro pose a model for signaling events induced by cyclic tensile stretch, namely a transmembrane mechanosensor which couples Gi-protein, actin cytoskeleton and finally activates JNK/SAPK activity of osteoblasts. (C) 2001 Orthopaed ic Research Society. Published by Elsevier Science Ltd. All rights reserved .