The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.
Aggrecan degradation in human articular cartilage explants is mediated by both ADAMTS‐4 and ADAMTS‐5
Abstract
Objective: Recent published studies have shown that cartilage from ADAMTS‐5–knockout mice, but not ADAMTS‐4– or ADAMTS‐1–knockout mice, is significantly protected from degradation. The present study was undertaken to evaluate the respective roles of these enzymes in human cartilage breakdown, using a small interfering RNA (siRNA) approach to assess the effects of inhibition of each enzyme in normal and osteoarthritic (OA) explants. Methods: The activities of siRNA specifically targeting ADAMTS‐1, ‐4, and ‐5 were assessed by transfection into primary human chondrocytes and cultured human cartilage explants. At 24 hours, a cytokine stimulus was applied to normal, but not OA, samples to initiate a catabolic response. At designated times, total RNA was isolated and gene expression was measured by quantitative real‐time reverse transcription–polymerase chain reaction. Aggrecan release and aggrecanase‐generated neoepitope formation were determined by dye binding analysis and Western blotting, respectively. Results: Human chondrocytes and explants were efficiently transfected with siRNA that specifically decreased the expression of each targeted gene. Suppression of ADAMTS‐4 and ADAMTS‐5, individually or in combination, attenuated the degradation of aggrecan in cytokine‐stimulated normal cartilage. A reduction in aggrecan degradation was also observed following siRNA‐mediated knockdown of either gene in unstimulated OA cartilage. In contrast, knockdown of ADAMTS‐1 failed to inhibit aggrecan loss. Conclusion: Despite the apparent dominant role of ADAMTS‐5 in genetically modified mice, our data suggest that both ADAMTS‐4 and ADAMTS‐5 contribute to the structural damage that characterizes human OA.
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Cites
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Deletion of active ADAMTS5 prevents cartilage degradation in a murine model of osteoarthritis
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Self-citationUnlocking the potential of the human genome with RNA interference
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ADAMTS5 is the major aggrecanase in mouse cartilage in vivo and in vitro
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Purification and Cloning of Aggrecanase-1: A Member of the ADAMTS Family of Proteins
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Self-citationCloning and Characterization of ADAMTS11 , an Aggrecanase from the ADAMTS Family
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Cited by
Inflammation in osteoarthritis
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Proteases involved in cartilage matrix degradation in osteoarthritis
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Hypoxia-inducible factor-2α is a catabolic regulator of osteoarthritic cartilage destruction
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Metadata
- Authors
- Song, R., D. Tortorella, M., Malfait, A., Alston, J. T., Yang, Z., Arner, E. C., & Griggs, D. W.
- Venue
- Arthritis & Rheumatism
- Publisher
- Wiley
- Published
- 2007-01-30
- Volume
- 56
- Issue
- 2
- Pages
- 575-585
- ISSN
- 0004-3591 (ISSN-L)
- 1529-0131
- OpenAlex
- W2012899141
- Cited by
- 405
- References
- 30
- FWCI
- 16.75
- Type
- journal article
- Language
- en
- Open access
- closed
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