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The catabolic pathway mediated by Toll-like receptors in human osteoarthritic chondrocytes.
Arthritis Rheum. 2006 Jul; 54(7):2152-63.AR

Abstract

OBJECTIVE

To examine the catabolic pathways mediated by Toll-like receptor (TLR) ligands in human osteoarthritic (OA) chondrocytes.

METHODS

The presence of TLRs in OA and non-OA articular cartilage was analyzed by immunohistochemistry. The regulation of TLR messenger RNA (mRNA) by interleukin-1 (IL-1) and tumor necrosis factor alpha (TNFalpha) was analyzed by reverse transcription-polymerase chain reaction. For stimulation of TLR-2 and TLR-4, chondrocytes were treated with Staphylococcus aureus peptidoglycan and lipopolysaccharides (LPS), respectively. Production of matrix metalloproteinases (MMPs) 1, 3, and 13 and prostaglandin E2 (PGE2) was evaluated by enzyme-linked immunosorbent assay. Production of nitric oxide (NO) was analyzed by the Griess reaction. Regulation of cyclooxygenase 2 protein and phosphorylation of MAPKs (p38, ERK, and JNK) were evaluated by Western blotting or solid-phase kinase assay. NF-kappaB activation was evaluated by electrophoretic mobility shift assay.

RESULTS

Expression of TLRs 2 and 4 was up-regulated in lesional areas of OA cartilage. Treatment with IL-1, TNFalpha, peptidoglycan, and LPS all significantly up-regulated TLR-2 mRNA expression in cultured chondrocytes. Production of MMPs 1, 3, and 13 and of NO and PGE2 was significantly increased after treating chondrocytes with either of the TLR ligands. Prolonged culture of cartilage explants with TLR ligands also led to a significant increase in the release of proteoglycan and type II collagen degradation product. Treatment with TLR ligands led to phosphorylation of all 3 MAPKs and activation of NF-kappaB.

CONCLUSION

We found that TLRs are increased in OA cartilage lesions. TLR-2 and TLR-4 ligands strongly induce catabolic responses in chondrocytes. Modulation of TLR-mediated signaling as a therapeutic strategy would require detailed elucidation of the signaling pathways involved.

Authors+Show Affiliations

Division of Rheumatology, Department of Internal Medicine, Hallym University Sacred Heart Hospital, 896, Pyongchon-dong, Dongan-gu, Anyang, Kyunggi-do 431-070, Republic of Korea. kimha@hallym.ac.krNo 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

16802353

Citation

Kim, Hyun Ah, et al. "The Catabolic Pathway Mediated By Toll-like Receptors in Human Osteoarthritic Chondrocytes." Arthritis and Rheumatism, vol. 54, no. 7, 2006, pp. 2152-63.
Kim HA, Cho ML, Choi HY, et al. The catabolic pathway mediated by Toll-like receptors in human osteoarthritic chondrocytes. Arthritis Rheum. 2006;54(7):2152-63.
Kim, H. A., Cho, M. L., Choi, H. Y., Yoon, C. S., Jhun, J. Y., Oh, H. J., & Kim, H. Y. (2006). The catabolic pathway mediated by Toll-like receptors in human osteoarthritic chondrocytes. Arthritis and Rheumatism, 54(7), 2152-63.
Kim HA, et al. The Catabolic Pathway Mediated By Toll-like Receptors in Human Osteoarthritic Chondrocytes. Arthritis Rheum. 2006;54(7):2152-63. PubMed PMID: 16802353.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The catabolic pathway mediated by Toll-like receptors in human osteoarthritic chondrocytes. AU - Kim,Hyun Ah, AU - Cho,Mi-La, AU - Choi,Hye Young, AU - Yoon,Chang Sik, AU - Jhun,Joo Yeon, AU - Oh,Hey Jwa, AU - Kim,Ho-Youn, PY - 2006/6/28/pubmed PY - 2006/9/14/medline PY - 2006/6/28/entrez SP - 2152 EP - 63 JF - Arthritis and rheumatism JO - Arthritis Rheum. VL - 54 IS - 7 N2 - OBJECTIVE: To examine the catabolic pathways mediated by Toll-like receptor (TLR) ligands in human osteoarthritic (OA) chondrocytes. METHODS: The presence of TLRs in OA and non-OA articular cartilage was analyzed by immunohistochemistry. The regulation of TLR messenger RNA (mRNA) by interleukin-1 (IL-1) and tumor necrosis factor alpha (TNFalpha) was analyzed by reverse transcription-polymerase chain reaction. For stimulation of TLR-2 and TLR-4, chondrocytes were treated with Staphylococcus aureus peptidoglycan and lipopolysaccharides (LPS), respectively. Production of matrix metalloproteinases (MMPs) 1, 3, and 13 and prostaglandin E2 (PGE2) was evaluated by enzyme-linked immunosorbent assay. Production of nitric oxide (NO) was analyzed by the Griess reaction. Regulation of cyclooxygenase 2 protein and phosphorylation of MAPKs (p38, ERK, and JNK) were evaluated by Western blotting or solid-phase kinase assay. NF-kappaB activation was evaluated by electrophoretic mobility shift assay. RESULTS: Expression of TLRs 2 and 4 was up-regulated in lesional areas of OA cartilage. Treatment with IL-1, TNFalpha, peptidoglycan, and LPS all significantly up-regulated TLR-2 mRNA expression in cultured chondrocytes. Production of MMPs 1, 3, and 13 and of NO and PGE2 was significantly increased after treating chondrocytes with either of the TLR ligands. Prolonged culture of cartilage explants with TLR ligands also led to a significant increase in the release of proteoglycan and type II collagen degradation product. Treatment with TLR ligands led to phosphorylation of all 3 MAPKs and activation of NF-kappaB. CONCLUSION: We found that TLRs are increased in OA cartilage lesions. TLR-2 and TLR-4 ligands strongly induce catabolic responses in chondrocytes. Modulation of TLR-mediated signaling as a therapeutic strategy would require detailed elucidation of the signaling pathways involved. SN - 0004-3591 UR - https://www.unboundmedicine.com/medline/citation/16802353/The_catabolic_pathway_mediated_by_Toll_like_receptors_in_human_osteoarthritic_chondrocytes_ L2 - https://doi.org/10.1002/art.21951 DB - PRIME DP - Unbound Medicine ER -