help button home button Endocrine Society Endocrinology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Schwartz, Z.
Right arrow Articles by Boyan, B. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Schwartz, Z.
Right arrow Articles by Boyan, B. D.
Endocrinology Vol. 140, No. 7 2991-3002
Copyright © 1999 by The Endocrine Society

ARTICLES

Arachidonic Acid Directly Mediates the Rapid Effects of 24,25-Dihydroxyvitamin D3 Via Protein Kinase C and Indirectly through Prostaglandin Production in Resting Zone Chondrocytes1

Z. Schwartz, V. L. Sylvia, D. Curry, M. H. Luna, D. D. Dean and B. D. Boyan

Departments of Orthopedics (Z.S., V.L.S., D.C., M.H.L., D.D.D., B.D.B.), Periodontics (Z.S., B.D.B.), and Biochemistry (B.D.B.), University of Texas Health Science Center, San Antonio, Texas 78284; Department of Periodontics, Lackland Air Force Base (D.C.), San Antonio, Texas 78236; and Department of Periodontics, Hebrew University Hadassah Faculty of Dental Medicine (Z.S.), Jerusalem, Israel 91010

Address all correspondence and requests for reprints to: Barbara D. Boyan, Ph.D., Department of Orthopedics, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, Texas 78284-7774. E-mail: boyanb{at}uthscsa.edu

Prior studies have shown that 24,25-dihydroxyvitamin D3 [24,25-(OH)2D3] plays a major role in resting zone chondrocyte differentiation and that this vitamin D metabolite regulates both phospholipase A2 and protein kinase C (PKC) specific activities. Arachidonic acid is the product of phospholipase A2 action and has been shown in other systems to affect a variety of cellular functions, including PKC activity. The aim of the present study was to examine the interrelationship between arachidonic acid and 24,25-(OH)2D3 on markers of proliferation, differentiation, and matrix production in resting zone chondrocytes and to characterize the mechanisms by which arachidonic acid regulates PKC, which was shown previously to mediate the rapid effects of 24,25-(OH)2D3 and arachidonic acid on these cells. Confluent, fourth passage resting zone cells from rat costochondral cartilage were used to evaluate these mechanisms. The addition of arachidonic acid to resting zone cultures stimulated [3H]thymidine incorporation and inhibited the activity of alkaline phosphatase and PKC, but had no effect on proteoglycan sulfation. In contrast, 24,25-(OH)2D3 inhibited [3H]thymidine incorporation and stimulated alkaline phosphatase, proteoglycan sulfation, and PKC activity. In cultures treated with both agents, the effects of 24,25-(OH)2D3 were reversed by arachidonic acid. The PKC isoform affected by arachidonic acid was PKC{alpha}; cytosolic levels were decreased, but membrane levels were unaffected, indicating that translocation did not occur. Arachidonic acid had a direct effect on PKC in isolated plasma membranes and matrix vesicles, indicating a nongenomic mechanism. Plasma membrane PKC{alpha} was inhibited, and matrix vesicle PKC{zeta} was stimulated; these effects were blocked by 24,25-(OH)2D3. Studies using cyclooxygenase and lipoxygenase inhibitors indicate that the effects of arachidonic acid are due in part to PG production, but not to leukotriene production. This is supported by the fact that H8-dependent inhibition of protein kinase A, which mediates the effects of PGE2, had no effect on the direct action of arachidonic acid but did mediate the role of arachidonic acid in the cell response to 24,25-(OH)2D3. Diacylglycerol does not appear to be involved, indicating that phospholipase C and/or D do not play a role. {gamma}-Linolenic acid, an unsaturated precursor of arachidonic acid, elicited a similar response in matrix vesicles but not plasma membranes, whereas palmitic acid, a saturated fatty acid, had no effect. These data suggest that arachidonic acid may act as a negative regulator of 24,25-(OH)2D3 action in resting zone chondrocytes.




This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
K. Mikule, S. Sunpaweravong, J. C. Gatlin, and K. H. Pfenninger
Eicosanoid Activation of Protein Kinase C {epsilon}: INVOLVEMENT IN GROWTH CONE REPELLENT SIGNALING
J. Biol. Chem., May 30, 2003; 278(23): 21168 - 21177.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
A. BONAZZI, M. BOLLA, C. BUCCELLATI, A. HERNANDEZ, S. ZARINI, T. VIGANÒ, F. FUMAGALLI, S. VIAPPIANI, S. RAVASI, P. ZANNINI, et al.
Effect of Endogenous and Exogenous Prostaglandin E2 on Interleukin-1{beta}-Induced Cyclooxygenase-2 Expression in Human Airway Smooth-Muscle Cells
Am. J. Respir. Crit. Care Med., December 1, 2000; 162(6): 2272 - 2277.
[Abstract] [Full Text]

Home page
 J. Biol. Chem.Home page
C. S. T. Hii, N. Moghadammi, A. Dunbar, and A. Ferrante
Activation of the Phosphatidylinositol 3-Kinase-Akt/Protein Kinase B Signaling Pathway in Arachidonic Acid-stimulated Human Myeloid and Endothelial Cells. INVOLVEMENT OF THE ErbB RECEPTOR FAMILY
J. Biol. Chem., July 13, 2001; 276(29): 27246 - 27255.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 1999 by The Endocrine Society