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PGE2 inhibits chondrocyte differentiation through PKA and PKC signaling.
Exp Cell Res. 2004 Oct 15; 300(1):159-69.EC

Abstract

Prostaglandins are ubiquitous metabolites of arachidonic acid, and cyclooxygenase inhibitors prevent their production and secretion. Animals with loss of cyclooxygenase-2 function have reduced reparative bone formation, but the role of prostaglandins during endochondral bone formation is not defined. The role of PGE2 as a regulator of chondrocyte differentiation in chick growth plate chondrocytes (GPCs) was examined. While PGE2, PGD2, PGF2alpha, and PGJ2 all inhibited colX expression, approximately 80% at 10(-6) M, PGE2 was the most potent activator of cAMP response element (CRE)-mediated transcription. PGE2 dose-dependently inhibited the expression of the differentiation-related genes, colX, VEGF, MMP-13, and alkaline phosphatase gene, and enzyme activity with significant effects at concentrations as low as 10(-10) M. PGE2 induced cyclic AMP response element binding protein (CREB) phosphorylation and increased c-Fos protein levels by 5 min, and activated transcription at CRE-Luc, AP-1-Luc, and c-Fos promoter constructs. The protein kinase A (PKA) inhibitor, H-89, completely blocked PGE2-mediated induction of CRE-Luc and c-Fos promoter-Luc promoters, and partially inhibited induction of AP-1-Luc, while the protein kinase C (PKC) inhibitor Go-6976 partially inhibited all three promoters, demonstrating substantial cross-talk between these signaling pathways. PGE2 inhibition of colX gene expression was dependent upon both PKA and PKC signaling. These observations demonstrate potent prostaglandin regulatory effects on chondrocyte maturation and show a role for both PKA and PKC signaling in PGE2 regulatory events.

Authors+Show Affiliations

Center for Musculoskeletal Research, School of Medicine and Dentistry, University of Rochester, Rochester, NY 14642, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15383323

Citation

Li, Tian-Fang, et al. "PGE2 Inhibits Chondrocyte Differentiation Through PKA and PKC Signaling." Experimental Cell Research, vol. 300, no. 1, 2004, pp. 159-69.
Li TF, Zuscik MJ, Ionescu AM, et al. PGE2 inhibits chondrocyte differentiation through PKA and PKC signaling. Exp Cell Res. 2004;300(1):159-69.
Li, T. F., Zuscik, M. J., Ionescu, A. M., Zhang, X., Rosier, R. N., Schwarz, E. M., Drissi, H., & O'Keefe, R. J. (2004). PGE2 inhibits chondrocyte differentiation through PKA and PKC signaling. Experimental Cell Research, 300(1), 159-69.
Li TF, et al. PGE2 Inhibits Chondrocyte Differentiation Through PKA and PKC Signaling. Exp Cell Res. 2004 Oct 15;300(1):159-69. PubMed PMID: 15383323.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - PGE2 inhibits chondrocyte differentiation through PKA and PKC signaling. AU - Li,Tian-Fang, AU - Zuscik,Michael J, AU - Ionescu,Andreia M, AU - Zhang,Xinping, AU - Rosier,Randy N, AU - Schwarz,Edward M, AU - Drissi,Hicham, AU - O'Keefe,Regis J, PY - 2004/04/07/received PY - 2004/06/17/revised PY - 2004/9/24/pubmed PY - 2004/12/16/medline PY - 2004/9/24/entrez SP - 159 EP - 69 JF - Experimental cell research JO - Exp Cell Res VL - 300 IS - 1 N2 - Prostaglandins are ubiquitous metabolites of arachidonic acid, and cyclooxygenase inhibitors prevent their production and secretion. Animals with loss of cyclooxygenase-2 function have reduced reparative bone formation, but the role of prostaglandins during endochondral bone formation is not defined. The role of PGE2 as a regulator of chondrocyte differentiation in chick growth plate chondrocytes (GPCs) was examined. While PGE2, PGD2, PGF2alpha, and PGJ2 all inhibited colX expression, approximately 80% at 10(-6) M, PGE2 was the most potent activator of cAMP response element (CRE)-mediated transcription. PGE2 dose-dependently inhibited the expression of the differentiation-related genes, colX, VEGF, MMP-13, and alkaline phosphatase gene, and enzyme activity with significant effects at concentrations as low as 10(-10) M. PGE2 induced cyclic AMP response element binding protein (CREB) phosphorylation and increased c-Fos protein levels by 5 min, and activated transcription at CRE-Luc, AP-1-Luc, and c-Fos promoter constructs. The protein kinase A (PKA) inhibitor, H-89, completely blocked PGE2-mediated induction of CRE-Luc and c-Fos promoter-Luc promoters, and partially inhibited induction of AP-1-Luc, while the protein kinase C (PKC) inhibitor Go-6976 partially inhibited all three promoters, demonstrating substantial cross-talk between these signaling pathways. PGE2 inhibition of colX gene expression was dependent upon both PKA and PKC signaling. These observations demonstrate potent prostaglandin regulatory effects on chondrocyte maturation and show a role for both PKA and PKC signaling in PGE2 regulatory events. SN - 0014-4827 UR - https://www.unboundmedicine.com/medline/citation/15383323/PGE2_inhibits_chondrocyte_differentiation_through_PKA_and_PKC_signaling_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4827(04)00362-3 DB - PRIME DP - Unbound Medicine ER -