Abstract
Cyclooxygenase (COX) is the key enzyme in the production of prostaglandins, which are essential for the response of bone to mechanical loading. We determined which COX-isoform, COX-1 or COX-2, determines loading-induced prostaglandin production in primary bone cells in vitro. Mouse and human bone cells reacted to 1 h of pulsating fluid flow (PFF, 0.6+/-0.3 Pa at 5 Hz) with an increased prostaglandin E(2) production, which continued 24 h after cessation of PFF. Inhibition of COX-2 activity with NS-398 abolished the stimulating effect of PFF both at 1 h and at 24 h post-incubation, while inhibition of COX-1 by SC-560 affected neither the early nor the late response to flow. PFF rapidly stimulated COX-2 mRNA expression at 1 h but did not affect COX-1 mRNA expression. COX-2 mRNA expression was still significantly enhanced 24 h after cessation of PFF. We conclude that COX-2 is the mechanosensitive form of COX that determines the response of bone tissue to mechanical loading.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Bone and Bones / cytology*
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Bone and Bones / drug effects
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Bone and Bones / enzymology*
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Cells, Cultured
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Cyclooxygenase 1
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Cyclooxygenase 2
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Cyclooxygenase 2 Inhibitors
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Cyclooxygenase Inhibitors / pharmacology
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Dinoprostone / biosynthesis
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Enzyme Activation
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Humans
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Isoenzymes / antagonists & inhibitors
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Isoenzymes / genetics
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Isoenzymes / metabolism*
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Mechanotransduction, Cellular*
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Membrane Proteins
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Mice
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Nitrobenzenes / pharmacology
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Prostaglandin-Endoperoxide Synthases / genetics
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Prostaglandin-Endoperoxide Synthases / metabolism*
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Pyrazoles / pharmacology
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RNA, Messenger / biosynthesis
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Stress, Mechanical
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Sulfonamides / pharmacology
Substances
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Cyclooxygenase 2 Inhibitors
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Cyclooxygenase Inhibitors
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Isoenzymes
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Membrane Proteins
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Nitrobenzenes
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Pyrazoles
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RNA, Messenger
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SC 560
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Sulfonamides
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N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
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Cyclooxygenase 1
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Cyclooxygenase 2
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PTGS1 protein, human
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PTGS2 protein, human
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Prostaglandin-Endoperoxide Synthases
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Ptgs1 protein, mouse
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Dinoprostone