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Effects of advanced glycation end products on the expression of COX-2, PGE2 and NO in human osteoarthritic chondrocytes.
Rheumatology (Oxford). 2008 Apr; 47(4):425-31.R

Abstract

OBJECTIVE

Advanced glycation end products (AGE) accumulate in articular cartilage with age. We investigated the effects of AGE in primary-cultured human OA chondrocytes.

METHODS

Chondrocytes were cultured with/or without AGE-bovine serum albumin (AGE-BSA) and the expression levels of inducible nitric oxide (iNOS), cyclooxygenase (COX)-2 microsomal prostaglandin E synthase-1 (mPGES-1) were evaluated using RT-PCR and western blot analysis. Prostaglandin E(2) (PGE(2)) was analysed by ELISA and nitric oxide (NO) was analysed by Griess reaction assay. Pharmacological studies to elucidate the involved pathway were executed using specific inhibitors of MAPK and receptor for AGE (RAGE).

RESULTS

We found that treatment of OA chondrocytes with AGE-BSA increased COX-2, mPGES-1 and iNOS mRNA and protein, as well as elevating production of PGE(2) and NO. Pre-treatment with the MAPK inhibitors SP600125 (JNK inhibitor), SB202190 (p38 inhibitor) or PD98059 (ERK inhibitor) significantly inhibited AGE-BSA induction of COX-2 expression and production of PGE(2). In contrast, SN50, a nuclear factor-kappaB (NF-kappaB) inhibitor, had no effect on levels of COX-2 and PGE(2). SB202190 and SN50, but not SP600125 and PD98059, decreased AGE-BSA-induced production of NO. Pre-treatment with soluble receptor for AGE (sRAGE) also reduced AGE-stimulated COX-2, iNOS and PGE(2), implicating the involvement of RAGE.

CONCLUSIONS

These results show that AGE may augment inflammatory responses in OA chondrocytes by increasing PGE(2) and NO levels, possibly via the MAPK pathway for PGE(2) and the NF-kappaB pathway for NO.

Authors+Show Affiliations

Division of Allergy and Rheumatology, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, 388-1, Pungnap-dong, Songpa-gu, Seoul 138-736, Korea.No 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, Non-U.S. Gov't

Language

eng

PubMed ID

18285354

Citation

Nah, S-S, et al. "Effects of Advanced Glycation End Products On the Expression of COX-2, PGE2 and NO in Human Osteoarthritic Chondrocytes." Rheumatology (Oxford, England), vol. 47, no. 4, 2008, pp. 425-31.
Nah SS, Choi IY, Lee CK, et al. Effects of advanced glycation end products on the expression of COX-2, PGE2 and NO in human osteoarthritic chondrocytes. Rheumatology (Oxford). 2008;47(4):425-31.
Nah, S. S., Choi, I. Y., Lee, C. K., Oh, J. S., Kim, Y. G., Moon, H. B., & Yoo, B. (2008). Effects of advanced glycation end products on the expression of COX-2, PGE2 and NO in human osteoarthritic chondrocytes. Rheumatology (Oxford, England), 47(4), 425-31. https://doi.org/10.1093/rheumatology/kem376
Nah SS, et al. Effects of Advanced Glycation End Products On the Expression of COX-2, PGE2 and NO in Human Osteoarthritic Chondrocytes. Rheumatology (Oxford). 2008;47(4):425-31. PubMed PMID: 18285354.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of advanced glycation end products on the expression of COX-2, PGE2 and NO in human osteoarthritic chondrocytes. AU - Nah,S-S, AU - Choi,I-Y, AU - Lee,C K, AU - Oh,J S, AU - Kim,Y G, AU - Moon,H-B, AU - Yoo,B, Y1 - 2008/02/19/ PY - 2008/2/21/pubmed PY - 2008/5/9/medline PY - 2008/2/21/entrez SP - 425 EP - 31 JF - Rheumatology (Oxford, England) JO - Rheumatology (Oxford) VL - 47 IS - 4 N2 - OBJECTIVE: Advanced glycation end products (AGE) accumulate in articular cartilage with age. We investigated the effects of AGE in primary-cultured human OA chondrocytes. METHODS: Chondrocytes were cultured with/or without AGE-bovine serum albumin (AGE-BSA) and the expression levels of inducible nitric oxide (iNOS), cyclooxygenase (COX)-2 microsomal prostaglandin E synthase-1 (mPGES-1) were evaluated using RT-PCR and western blot analysis. Prostaglandin E(2) (PGE(2)) was analysed by ELISA and nitric oxide (NO) was analysed by Griess reaction assay. Pharmacological studies to elucidate the involved pathway were executed using specific inhibitors of MAPK and receptor for AGE (RAGE). RESULTS: We found that treatment of OA chondrocytes with AGE-BSA increased COX-2, mPGES-1 and iNOS mRNA and protein, as well as elevating production of PGE(2) and NO. Pre-treatment with the MAPK inhibitors SP600125 (JNK inhibitor), SB202190 (p38 inhibitor) or PD98059 (ERK inhibitor) significantly inhibited AGE-BSA induction of COX-2 expression and production of PGE(2). In contrast, SN50, a nuclear factor-kappaB (NF-kappaB) inhibitor, had no effect on levels of COX-2 and PGE(2). SB202190 and SN50, but not SP600125 and PD98059, decreased AGE-BSA-induced production of NO. Pre-treatment with soluble receptor for AGE (sRAGE) also reduced AGE-stimulated COX-2, iNOS and PGE(2), implicating the involvement of RAGE. CONCLUSIONS: These results show that AGE may augment inflammatory responses in OA chondrocytes by increasing PGE(2) and NO levels, possibly via the MAPK pathway for PGE(2) and the NF-kappaB pathway for NO. SN - 1462-0332 UR - https://www.unboundmedicine.com/medline/citation/18285354/Effects_of_advanced_glycation_end_products_on_the_expression_of_COX_2_PGE2_and_NO_in_human_osteoarthritic_chondrocytes_ L2 - https://academic.oup.com/rheumatology/article-lookup/doi/10.1093/rheumatology/kem376 DB - PRIME DP - Unbound Medicine ER -