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Estrogen receptor-related receptor α regulation by interleukin-1β in prostaglandin E(2)- and cAMP-dependent pathways in osteoarthritic chondrocytes.
Arthritis Rheum. 2011 Aug; 63(8):2374-84.AR

Abstract

OBJECTIVE

We reported previously that the orphan nuclear receptor, estrogen receptor-related receptor α (ERRα), is expressed in articular chondrocytes and is dysregulated in a mouse model of inflammatory arthritis. The aim of this study, therefore, was to determine whether ERRα is also dysregulated in patients with osteoarthritis (OA).

METHODS

ERRα messenger RNA (mRNA) and protein were quantified in normal and OA cartilage samples and in OA chondrocytes in vitro, with and without short-term treatment with a variety of OA-associated factors and signaling pathway agonists and inhibitors.

RESULTS

ERRα expression was lower in OA than in normal articular cartilage. Interleukin-1β (IL-1β) markedly up-regulated ERRα expression in OA chondrocytes in vitro, and agonist or inhibitor treatment indicated that the up-regulation was dependent on cyclooxygenase 2 (COX-2; NS398), prostaglandin E(2), cAMP (8-bromo-cAMP), and protein kinase A (PKA; KT5720). Treatment with the ERRα inverse agonist XCT790 decreased the expression of SOX9 and the up-regulation of ERRα by IL-1β, suggesting autoregulation of ERRα in the IL-1β pathway. Matrix metalloproteinase 13 (MMP-13) expression was also decreased by treatment with XCT790 plus IL-1β versus IL-1β alone, and the down-regulation of MMP-13 mRNA and protein observed with XCT790 alone suggests that the up-regulation of MMP-13 by IL-1β is ERRα-dependent.

CONCLUSION

We report the first evidence that ERRα expression is regulated by IL-1β in COX-2-, cAMP-, and PKA-dependent pathways in OA chondrocytes. We confirmed that SOX9 is an ERRα target gene in human, as in rodent, chondrocytes and identified MMP-13 as a potential new target gene, which suggests that ERRα may both respond to the healing signal and contribute to extracellular degradation in OA cartilage.

Authors+Show Affiliations

INSERM U664, Lyon, France. edith.bonnelye@inserm.frNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

21506092

Citation

Bonnelye, Edith, et al. "Estrogen Receptor-related Receptor Α Regulation By Interleukin-1β in Prostaglandin E(2)- and cAMP-dependent Pathways in Osteoarthritic Chondrocytes." Arthritis and Rheumatism, vol. 63, no. 8, 2011, pp. 2374-84.
Bonnelye E, Reboul P, Duval N, et al. Estrogen receptor-related receptor α regulation by interleukin-1β in prostaglandin E(2)- and cAMP-dependent pathways in osteoarthritic chondrocytes. Arthritis Rheum. 2011;63(8):2374-84.
Bonnelye, E., Reboul, P., Duval, N., Cardelli, M., & Aubin, J. E. (2011). Estrogen receptor-related receptor α regulation by interleukin-1β in prostaglandin E(2)- and cAMP-dependent pathways in osteoarthritic chondrocytes. Arthritis and Rheumatism, 63(8), 2374-84. https://doi.org/10.1002/art.30398
Bonnelye E, et al. Estrogen Receptor-related Receptor Α Regulation By Interleukin-1β in Prostaglandin E(2)- and cAMP-dependent Pathways in Osteoarthritic Chondrocytes. Arthritis Rheum. 2011;63(8):2374-84. PubMed PMID: 21506092.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Estrogen receptor-related receptor α regulation by interleukin-1β in prostaglandin E(2)- and cAMP-dependent pathways in osteoarthritic chondrocytes. AU - Bonnelye,Edith, AU - Reboul,Pascal, AU - Duval,Nicolas, AU - Cardelli,Marco, AU - Aubin,Jane E, PY - 2011/4/21/entrez PY - 2011/4/21/pubmed PY - 2011/11/1/medline SP - 2374 EP - 84 JF - Arthritis and rheumatism JO - Arthritis Rheum. VL - 63 IS - 8 N2 - OBJECTIVE: We reported previously that the orphan nuclear receptor, estrogen receptor-related receptor α (ERRα), is expressed in articular chondrocytes and is dysregulated in a mouse model of inflammatory arthritis. The aim of this study, therefore, was to determine whether ERRα is also dysregulated in patients with osteoarthritis (OA). METHODS: ERRα messenger RNA (mRNA) and protein were quantified in normal and OA cartilage samples and in OA chondrocytes in vitro, with and without short-term treatment with a variety of OA-associated factors and signaling pathway agonists and inhibitors. RESULTS: ERRα expression was lower in OA than in normal articular cartilage. Interleukin-1β (IL-1β) markedly up-regulated ERRα expression in OA chondrocytes in vitro, and agonist or inhibitor treatment indicated that the up-regulation was dependent on cyclooxygenase 2 (COX-2; NS398), prostaglandin E(2), cAMP (8-bromo-cAMP), and protein kinase A (PKA; KT5720). Treatment with the ERRα inverse agonist XCT790 decreased the expression of SOX9 and the up-regulation of ERRα by IL-1β, suggesting autoregulation of ERRα in the IL-1β pathway. Matrix metalloproteinase 13 (MMP-13) expression was also decreased by treatment with XCT790 plus IL-1β versus IL-1β alone, and the down-regulation of MMP-13 mRNA and protein observed with XCT790 alone suggests that the up-regulation of MMP-13 by IL-1β is ERRα-dependent. CONCLUSION: We report the first evidence that ERRα expression is regulated by IL-1β in COX-2-, cAMP-, and PKA-dependent pathways in OA chondrocytes. We confirmed that SOX9 is an ERRα target gene in human, as in rodent, chondrocytes and identified MMP-13 as a potential new target gene, which suggests that ERRα may both respond to the healing signal and contribute to extracellular degradation in OA cartilage. SN - 1529-0131 UR - https://www.unboundmedicine.com/medline/citation/21506092/Estrogen_receptor_related_receptor_α_regulation_by_interleukin_1β_in_prostaglandin_E_2___and_cAMP_dependent_pathways_in_osteoarthritic_chondrocytes_ L2 - https://doi.org/10.1002/art.30398 DB - PRIME DP - Unbound Medicine ER -