期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 297, 期 1, 页码 46-51出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/S0006-291X(02)02124-1
关键词
prostaglandins; signal transduction; cyclooxygenase; mechanical loading; bone
资金
- NIAMS NIH HHS [R01-AR47673] Funding Source: Medline
Mechanical loading of bone generates fluid flow within the mineralized matrix which can exert fluid shear stress (FSS) at cell membranes. FSS induces new transcription of cyclooxygenase-2 (COX-2) in MC3T3-E1 osteoblasts, with peak effects at 4-5 h. Using MC3T3-E1 cells stably transfected with the COX-2 promoter fused to a luciferase reporter, we examined involvement of the protein kinase A (PKA) and protein kinase C (PKC) signaling pathways in the peak COX-2 mRNA and luciferase responses to FSS (10 dyn/cm(2)). Neither inhibition nor down-regulation of the PKC pathway affected the FSS stimulation of COX-2 mRNA or luciferase activity. In contrast, inhibitors of the PKA pathway, used at doses which inhibited forskolin-stimulated luciferase activity by 70-80%, reduced FSS-stimulated COX-2 mRNA expression and luciferase activity by 50-80%. Hence, peak FSS induction of COX-2 expression in MC3T3-E1 osteoblastic cells is largely dependent on the PKA signaling pathway. (C) 2002 Elsevier Science (USA). All rights reserved.
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