Tenascin-C induces inflammatory mediators and matrix degradation in osteoarthritic cartilage
<p>Abstract</p> <p>Background</p> <p>Tenascin-C (TN-C) is an extracellular matrix glycoprotein that is involved in tissue injury and repair processes. We analyzed TN-C expression in normal and osteoarthritic (OA) human cartilage, and evaluated its capacity to induce inf...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2011-07-01
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| Series: | BMC Musculoskeletal Disorders |
| Online Access: | http://www.biomedcentral.com/1471-2474/12/164 |
| _version_ | 1818348879529115648 |
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| author | Flannery Carl R Morris Elisabeth A Glasson Sonya S Sun Weiyong Patel Lisha Chockalingam Priya S |
| author_facet | Flannery Carl R Morris Elisabeth A Glasson Sonya S Sun Weiyong Patel Lisha Chockalingam Priya S |
| author_sort | Flannery Carl R |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Tenascin-C (TN-C) is an extracellular matrix glycoprotein that is involved in tissue injury and repair processes. We analyzed TN-C expression in normal and osteoarthritic (OA) human cartilage, and evaluated its capacity to induce inflammatory and catabolic mediators in chondrocytes <it>in vitro</it>. The effect of TN-C on proteoglycan loss from articular cartilage in culture was also assessed.</p> <p>Methods</p> <p>TN-C in culture media, cartilage extracts, and synovial fluid of human and animal joints was quantified using a sandwich ELISA and/or analyzed by Western immunoblotting. mRNA expression of TN-C and aggrecanases were analyzed by Taqman assays. Human and bovine primary chondrocytes and/or explant culture systems were utilized to study TN-C induced inflammatory or catabolic mediators and proteoglycan loss. Total proteoglycan and aggrecanase -generated ARG-aggrecan fragments were quantified in human and rat synovial fluids by ELISA.</p> <p>Results</p> <p>TN-C protein and mRNA expression were significantly upregulated in OA cartilage with a concomitant elevation of TN-C levels in the synovial fluid of OA patients. IL-1 enhanced TN-C expression in articular cartilage. Addition of TN-C induced IL-6, PGE<sub>2</sub>, and nitrate release and upregulated ADAMTS4 mRNA in cultured primary human and bovine chondrocytes. TN-C treatment resulted in an increased loss of proteoglycan from cartilage explants in culture. A correlation was observed between TN-C and aggrecanase generated ARG-aggrecan fragment levels in the synovial fluid of human OA joints and in the lavage of rat joints that underwent surgical induction of OA.</p> <p>Conclusions</p> <p>TN-C expression in the knee cartilage and TN-C levels measured in the synovial fluid are significantly enhanced in OA patients. Our findings suggest that the elevated levels of TN-C could induce inflammatory mediators and promote matrix degradation in OA joints.</p> |
| first_indexed | 2024-12-13T17:57:04Z |
| format | Article |
| id | doaj.art-f91308049a4a45ad86f25e4e3535c776 |
| institution | Directory Open Access Journal |
| issn | 1471-2474 |
| language | English |
| last_indexed | 2024-12-13T17:57:04Z |
| publishDate | 2011-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Musculoskeletal Disorders |
| spelling | doaj.art-f91308049a4a45ad86f25e4e3535c7762022-12-21T23:36:20ZengBMCBMC Musculoskeletal Disorders1471-24742011-07-0112116410.1186/1471-2474-12-164Tenascin-C induces inflammatory mediators and matrix degradation in osteoarthritic cartilageFlannery Carl RMorris Elisabeth AGlasson Sonya SSun WeiyongPatel LishaChockalingam Priya S<p>Abstract</p> <p>Background</p> <p>Tenascin-C (TN-C) is an extracellular matrix glycoprotein that is involved in tissue injury and repair processes. We analyzed TN-C expression in normal and osteoarthritic (OA) human cartilage, and evaluated its capacity to induce inflammatory and catabolic mediators in chondrocytes <it>in vitro</it>. The effect of TN-C on proteoglycan loss from articular cartilage in culture was also assessed.</p> <p>Methods</p> <p>TN-C in culture media, cartilage extracts, and synovial fluid of human and animal joints was quantified using a sandwich ELISA and/or analyzed by Western immunoblotting. mRNA expression of TN-C and aggrecanases were analyzed by Taqman assays. Human and bovine primary chondrocytes and/or explant culture systems were utilized to study TN-C induced inflammatory or catabolic mediators and proteoglycan loss. Total proteoglycan and aggrecanase -generated ARG-aggrecan fragments were quantified in human and rat synovial fluids by ELISA.</p> <p>Results</p> <p>TN-C protein and mRNA expression were significantly upregulated in OA cartilage with a concomitant elevation of TN-C levels in the synovial fluid of OA patients. IL-1 enhanced TN-C expression in articular cartilage. Addition of TN-C induced IL-6, PGE<sub>2</sub>, and nitrate release and upregulated ADAMTS4 mRNA in cultured primary human and bovine chondrocytes. TN-C treatment resulted in an increased loss of proteoglycan from cartilage explants in culture. A correlation was observed between TN-C and aggrecanase generated ARG-aggrecan fragment levels in the synovial fluid of human OA joints and in the lavage of rat joints that underwent surgical induction of OA.</p> <p>Conclusions</p> <p>TN-C expression in the knee cartilage and TN-C levels measured in the synovial fluid are significantly enhanced in OA patients. Our findings suggest that the elevated levels of TN-C could induce inflammatory mediators and promote matrix degradation in OA joints.</p>http://www.biomedcentral.com/1471-2474/12/164 |
| spellingShingle | Flannery Carl R Morris Elisabeth A Glasson Sonya S Sun Weiyong Patel Lisha Chockalingam Priya S Tenascin-C induces inflammatory mediators and matrix degradation in osteoarthritic cartilage BMC Musculoskeletal Disorders |
| title | Tenascin-C induces inflammatory mediators and matrix degradation in osteoarthritic cartilage |
| title_full | Tenascin-C induces inflammatory mediators and matrix degradation in osteoarthritic cartilage |
| title_fullStr | Tenascin-C induces inflammatory mediators and matrix degradation in osteoarthritic cartilage |
| title_full_unstemmed | Tenascin-C induces inflammatory mediators and matrix degradation in osteoarthritic cartilage |
| title_short | Tenascin-C induces inflammatory mediators and matrix degradation in osteoarthritic cartilage |
| title_sort | tenascin c induces inflammatory mediators and matrix degradation in osteoarthritic cartilage |
| url | http://www.biomedcentral.com/1471-2474/12/164 |
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