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 significant role in mechanotransduction. We found the involvement of guanine-nucleotide-binding regulatory proteins (G proteins), especially Gi, in stress-inhibited NO release of osteoblast-like cells (JOR:17;593-597, 1999). To determine further the mechanism involved in this process, we measured c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) activity under cyclic tensile stretch loaded on osteoblast-like cells. Cyclic stretch significantly enhanced JNK/SAPK activity and pertussis toxin clearly reversed stress-enhanced JNK/SAPK activity. Cytochalasin D, actin microfilament disrupting reagent, also abolished the stress activation of JNK/SAPK. We propose 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.
Hara
F
F
Department of Orthopaedic Surgery, Kinki University, School of Medicine, Osaka, Japan.
Fukuda
K
K
Asada
S
S
Matsukawa
M
M
Hamanishi
C
C
D000199:Actins / Q000502:physiology*; D000818:Animals; D003599:Cytoskeleton / Q000502:physiology; D019204:GTP-Binding Proteins / Q000502:physiology*; D048031:JNK Mitogen-Activated Protein Kinases; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D010006:Osteoblasts / Q000378:metabolism*; D051381:Rats; D013718:Tensile Strength; D014407:Tumor Cells, Cultured
D000199:Actins; D009569:Nitric Oxide; D048031:JNK Mitogen-Activated Protein Kinases; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases; D019204:GTP-Binding Proteins