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Increased expression of lipocalin-type prostaglandin D2 synthase in osteoarthritic cartilage.
Arthritis Res Ther. 2008; 10(6):R146.AR

Abstract

INTRODUCTION

Prostaglandin D synthase (PGDS) is responsible for the biosynthesis of PGD and J series, which have been shown to exhibit anti-inflammatory and anticatabolic effects. Two isoforms have been identified: hematopoietic- and lipocalin-type PGDS (H-PGDS and L-PGDS, respectively). The aims of this study were to investigate the expressions of H-PGDS and L-PGDS in cartilage from healthy donors and from patients with osteoarthritis (OA) and to characterize their regulation by interleukin-1-beta (IL-1beta) in cultured OA chondrocytes.

METHODS

The expressions of H-PGDS and L-PGDS mRNA and protein in cartilage were analyzed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry, respectively. Chondrocytes were stimulated with IL-1beta, and the expression of L-PGDS was evaluated by real-time RT-PCR and Western blotting. The roles of de novo protein synthesis and of the signalling pathways mitogen-activated protein kinases (MAPKs), nuclear factor-kappa-B (NF-kappaB), and Notch were evaluated using specific pharmacological inhibitors.

RESULTS

L-PGDS and H-PGDS mRNAs were present in both healthy and OA cartilage, with higher levels of L-PGDS than H-PGDS (> 20-fold). The levels of L-PGDS mRNA and protein were increased in OA compared with healthy cartilage. Treatment of chondrocytes with IL-1beta upregulated L-PGDS mRNA and protein expressions as well as PGD2 production in a dose- and time-dependent manner. The upregulation of L-PGDS by IL-1beta was blocked by the translational inhibitor cycloheximide, indicating that this effect is indirect, requiring de novo protein synthesis. Specific inhibitors of the MAPK p38 (SB 203580) and c-jun N-terminal kinase (JNK) (SP600125) and of the NF-kappaB (SN-50) and Notch (DAPT) signalling pathways suppressed IL-1beta-induced upregulation of L-PGDS expression. In contrast, an inhibitor of the extracellular signal-regulated kinase (ERK/MAPK) (PD98059) demonstrated no significant influence. We also found that PGD2 prevented IL-1beta-induced upregulation of L-PGDS expression.

CONCLUSIONS

This is the first report demonstrating increased levels of L-PGDS in OA cartilage. IL-1beta may be responsible for this upregulation through activation of the JNK and p38 MAPK and NF-kappaB signalling pathways. These data suggest that L-PGDS might have an important role in the pathophysiology of OA.

Authors+Show Affiliations

Osteoarthritis Research Unit, Research Centre of the University of Montreal Hospital Center, Notre-Dame Hospital, Montreal, QC, Canada. nadia.zayed@umontreal.caNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19094210

Citation

Zayed, Nadia, et al. "Increased Expression of Lipocalin-type Prostaglandin D2 Synthase in Osteoarthritic Cartilage." Arthritis Research & Therapy, vol. 10, no. 6, 2008, pp. R146.
Zayed N, Li X, Chabane N, et al. Increased expression of lipocalin-type prostaglandin D2 synthase in osteoarthritic cartilage. Arthritis Res Ther. 2008;10(6):R146.
Zayed, N., Li, X., Chabane, N., Benderdour, M., Martel-Pelletier, J., Pelletier, J. P., Duval, N., & Fahmi, H. (2008). Increased expression of lipocalin-type prostaglandin D2 synthase in osteoarthritic cartilage. Arthritis Research & Therapy, 10(6), R146. https://doi.org/10.1186/ar2581
Zayed N, et al. Increased Expression of Lipocalin-type Prostaglandin D2 Synthase in Osteoarthritic Cartilage. Arthritis Res Ther. 2008;10(6):R146. PubMed PMID: 19094210.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Increased expression of lipocalin-type prostaglandin D2 synthase in osteoarthritic cartilage. AU - Zayed,Nadia, AU - Li,Xinfang, AU - Chabane,Nadir, AU - Benderdour,Mohamed, AU - Martel-Pelletier,Johanne, AU - Pelletier,Jean-Pierre, AU - Duval,Nicolas, AU - Fahmi,Hassan, Y1 - 2008/12/18/ PY - 2008/09/12/received PY - 2008/12/02/revised PY - 2008/12/18/accepted PY - 2008/12/20/entrez PY - 2008/12/20/pubmed PY - 2009/8/4/medline SP - R146 EP - R146 JF - Arthritis research & therapy JO - Arthritis Res. Ther. VL - 10 IS - 6 N2 - INTRODUCTION: Prostaglandin D synthase (PGDS) is responsible for the biosynthesis of PGD and J series, which have been shown to exhibit anti-inflammatory and anticatabolic effects. Two isoforms have been identified: hematopoietic- and lipocalin-type PGDS (H-PGDS and L-PGDS, respectively). The aims of this study were to investigate the expressions of H-PGDS and L-PGDS in cartilage from healthy donors and from patients with osteoarthritis (OA) and to characterize their regulation by interleukin-1-beta (IL-1beta) in cultured OA chondrocytes. METHODS: The expressions of H-PGDS and L-PGDS mRNA and protein in cartilage were analyzed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry, respectively. Chondrocytes were stimulated with IL-1beta, and the expression of L-PGDS was evaluated by real-time RT-PCR and Western blotting. The roles of de novo protein synthesis and of the signalling pathways mitogen-activated protein kinases (MAPKs), nuclear factor-kappa-B (NF-kappaB), and Notch were evaluated using specific pharmacological inhibitors. RESULTS: L-PGDS and H-PGDS mRNAs were present in both healthy and OA cartilage, with higher levels of L-PGDS than H-PGDS (> 20-fold). The levels of L-PGDS mRNA and protein were increased in OA compared with healthy cartilage. Treatment of chondrocytes with IL-1beta upregulated L-PGDS mRNA and protein expressions as well as PGD2 production in a dose- and time-dependent manner. The upregulation of L-PGDS by IL-1beta was blocked by the translational inhibitor cycloheximide, indicating that this effect is indirect, requiring de novo protein synthesis. Specific inhibitors of the MAPK p38 (SB 203580) and c-jun N-terminal kinase (JNK) (SP600125) and of the NF-kappaB (SN-50) and Notch (DAPT) signalling pathways suppressed IL-1beta-induced upregulation of L-PGDS expression. In contrast, an inhibitor of the extracellular signal-regulated kinase (ERK/MAPK) (PD98059) demonstrated no significant influence. We also found that PGD2 prevented IL-1beta-induced upregulation of L-PGDS expression. CONCLUSIONS: This is the first report demonstrating increased levels of L-PGDS in OA cartilage. IL-1beta may be responsible for this upregulation through activation of the JNK and p38 MAPK and NF-kappaB signalling pathways. These data suggest that L-PGDS might have an important role in the pathophysiology of OA. SN - 1478-6362 UR - https://www.unboundmedicine.com/medline/citation/19094210/Increased_expression_of_lipocalin_type_prostaglandin_D2_synthase_in_osteoarthritic_cartilage_ L2 - https://arthritis-research.biomedcentral.com/articles/10.1186/ar2581 DB - PRIME DP - Unbound Medicine ER -