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Protein kinase C mediates flow-induced prostaglandin E2 production in osteoblasts (1993)

Reich, Kathleen M. ; Frangos, John A.

Springer

Calcified tissue international 52 (1993), S. 62-66

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ISSN: 1432-0827

Keywords: Signal transduction ; Bone remodeling ; Shear stress

Source: Springer Online Journal Archives 1860-2000

Topics: Biology , Medicine , Physics

Notes: Summary Interstitial fluid flow generated by skeletal loading may be responsible for load-induced bone remodeling. Production of prostaglandin E2 (PGE2), a potent mediator of bone remodeling, is augmented in osteoblasts exposed to fluid flow. Exposure to fluid flow resulted in a slight initial increase in PGE2 production (1–2 hour), followed by a dramatic increase (2–8 hours). The initial phase of only slightly increased PGE2 production was dependent on substrate availability. H7, a protein kinase C inhibitor, strongly inhibited flow-induced prostaglandin E2 production at all time points examined without effecting production in stationary cultures. Blocking protein synthesis with cycloheximide resulted in a 56% reduction in long-term flow-induced PGE2 production. Thus, the later phase appeared to be the result of an increased number of enzymes as well as increased activity of existing enzymes or increased substrate availability. In conclusion, fluid flow increases PGE2 production in osteoplasts via a protein kinase C-dependent pathway involvingde novo protein synthesis.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF00675628

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Fluid shear stress as a mediator of osteoblast cyclic adenosine monophosphate production (1990)

Reich, Kathleen M. ; Gay, Carol V. ; Frangos, John A.

New York, NY [u.a.] : Wiley-Blackwell

Journal of Cellular Physiology 143 (1990), S. 100-104

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ISSN: 0021-9541

Keywords: Life and Medical Sciences ; Cell & Developmental Biology

Source: Wiley InterScience Backfile Collection 1832-2000

Topics: Biology , Medicine

Notes: Effects of interstitial fluid flow on osteoblasts were investigated. Intracellular cyclic adenosine monophosphate (cAMP) levels were monitored in cultured osteo-blasts subjected to shear rates ranging from 10 to 3,500 sec-1. Cyclic AMP levels were significantly increased at all shear rates from 1 pmole/mg protein to 10-16 pmole/mg protein. Osteoblasts subjected to a shear rate of 430 sec-1 for 0.5-15 minutes exhibited elevated levels (12-fold) of intracellular cAMP, which were sustained throughout the perfusion period. Osteoblasts were three times more sensitive to flow stimulation than human umbilical vein endothelial cells and baby hamster kidney fibroblasts, which also displayed higher cAMP levels (4-fold) after exposure to flow. To distinguish streaming potential effects from shear stress effects, viscosity was increased 5-fold by addition of neutral dextran to the perfusing medium. Shear stress is a function of viscosity, and streaming potentials are not for a given shear rate. The mechanism of this cellular response to flow was shown to be shear stress dependent. Inhibition of cyclooxygenase by 20 μM ibuprofen completely inhibited the flow-dependent cAMP response, indicating the cAMP response is mediated by prostaglandins. Our results suggest that fluid flow induced by mechanical stress may be an important mediator of bone remodeling.

Additional Material: 5 Ill.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1002/jcp.1041430113

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