Toll-like receptors and chondrocytes: The lipopolysaccharide-induced decrease in cartilage matrix synthesis is dependent on the presence of toll-like receptor 4 and antagonized by bone morphogenetic protein 7
| العنوان: | Toll-like receptors and chondrocytes: The lipopolysaccharide-induced decrease in cartilage matrix synthesis is dependent on the presence of toll-like receptor 4 and antagonized by bone morphogenetic protein 7 |
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| المؤلفون: | Jochen G. Hofstaetter, Josef S Smolen, C. D. Toma, Shizuo Akira, Thomas Weichhart, Marcus D. Säemann, Ilse-Gerlinde Sunk, L. Amoyo, K. Bobacz |
| المصدر: | Arthritis & Rheumatism. 56:1880-1893 |
| بيانات النشر: | Wiley, 2007. |
| سنة النشر: | 2007 |
| مصطلحات موضوعية: | Adult, Lipopolysaccharides, Adolescent, Bone Morphogenetic Protein 7, Interleukin-1beta, Immunology, Type II collagen, Cartilage Oligomeric Matrix Protein, Biology, p38 Mitogen-Activated Protein Kinases, Chondrocyte, Mice, Chondrocytes, Rheumatology, Transforming Growth Factor beta, medicine, Animals, Humans, Matrilin Proteins, Immunology and Allergy, Pharmacology (medical), RNA, Messenger, Cells, Cultured, Aggrecan, Aged, Glycoproteins, Aged, 80 and over, Mice, Knockout, Cartilage oligomeric matrix protein, Extracellular Matrix Proteins, Toll-like receptor, Cartilage, Toll-Like Receptors, Middle Aged, Chondrogenesis, Cell biology, Mice, Inbred C57BL, Toll-Like Receptor 4, Bone morphogenetic protein 7, Interleukin 1 Receptor Antagonist Protein, medicine.anatomical_structure, Gene Expression Regulation, Bone Morphogenetic Proteins, biology.protein, Female |
| الوصف: | Objective To assess the presence of Toll-like receptors (TLRs) 1–9 in human articular cartilage, and to investigate the effects of lipopolysaccharide (LPS)–induced activation of TLR-4 on biosynthetic activity and matrix production by human articular chondrocytes. Methods TLRs 1–9 were assessed in human articular cartilage by reverse transcription–polymerase chain reaction (RT-PCR); TLR-4 was also analyzed by Western blotting and immunohistochemistry. Articular chondrocytes were isolated from human donors and from wild-type or TLR-4−/− mice. Chondrocyte monolayer cultures were incubated with interleukin-1β (IL-1β) and LPS in the absence or presence of bone morphogenetic protein 7 (BMP-7) and IL-1 receptor antagonist (IL-1Ra). Neosynthesis of sulfated glycosaminoglycans (sGAG) was measured by 35S-sulfate incorporation. Endogenous gene expression of cartilage markers as well as IL-1β was examined using RT-PCR. The involvement of p38 kinase or p44/42 kinase (ERK-1/2) in LPS-mediated TLR-4 signaling was investigated by immunoblotting, RT-PCR, and sGAG synthesis. Results TLRs 1–9 were found on the messenger RNA (mRNA) level in human articular chondrocytes. The presence of TLR-4 was also observed on the protein level. In murine and human articular chondrocytes, but not in chondrocytes derived from TLR-4−/− mice, stimulation with LPS resulted in a decrease in total proteoglycan synthesis. IL-1β mRNA expression was increased by TLR-4 activation, whereas expression of aggrecan and type II collagen was significantly decreased. The presence of BMP-7 and IL-1Ra antagonized the anti-anabolic effects of LPS. Blocking of p38, but not ERK-1/2, resulted in inhibition of both LPS-mediated IL-1β gene expression and the negative effects of LPS on matrix biosynthesis. Conclusion These data demonstrate the presence of TLRs in human articular cartilage. The suppressive effects of LPS on cartilage biosynthetic activity are dependent on the presence of TLR-4, are governed, at least in part, by an up-regulation of IL-1β, and are mediated by p38 kinase. These in vitro data indicate an anti-anabolic effect of TLR-4 in articular chondrocytes that may hamper cartilage repair in various joint diseases. |
| تدمد: | 1529-0131 0004-3591 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5282316c147b3295338ad4e5779b42c4Test https://doi.org/10.1002/art.22637Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....5282316c147b3295338ad4e5779b42c4 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15290131 00043591 |
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