Sulforaphane represses matrix-degrading proteases and protects cartilage from destruction in vitro and in vivo
Davidson RK, Jupp O, de Ferrars R, Kay CD, Culley KL, Norton R, Driscoll C, Vincent TL, Donell ST, Bao Y, Clark IM
Arthritis and rheumatism · 71 citas
Cómo se estudió
- Diseño
- Estudio in vitro o de mecanismos (clasificado por nuestro filtro de IA)
- Estudiado en
- Personas, más trabajo en animales o laboratorio
- Resultado principal
- Marcadores de salud y funcionamiento
Quién lo pagó
- Financiación
- Financiación independiente
- Organización sin fines de lucro
- Dunhill Medical Trust
- Universidad u hospital
- University of East Anglia
- Organización sin fines de lucro
- Versus Arthritis
- Gobierno
- Directorate for Biological Sciences
- Gobierno
- Biotechnology and Biological Sciences Research Council
- Subvenciones
- Versus Arthritis (19371); Biotechnology and Biological Sciences Research Council (BB/I006060/1); Biotechnology and Biological Sciences Research Council (BB/I006060/1); Versus Arthritis (20246)
Según 5 financiadores declarados.
Publicación
- Publicado
- 2013-08-27 · Arthritis Rheum · vol. 65 · número 12 · págs. 3130–3140
- Editorial
- Wiley
- Citado
- 84 citas · más que el 94% de estudios similares · 4.2× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 54 trabajos
- Acceso
- Acceso abierto (revista híbrida) · CC-BY
- Áreas de investigación
- Osteoarthritis Treatment and Mechanisms · Genomics, phytochemicals, and oxidative stress · Rheumatoid Arthritis Research and Therapies
- Palabras clave
- Sulforaphane, Cartilage, Matrix metalloproteinase, Cell biology, Chemistry, Osteoarthritis, Cancer research, Molecular biology, Biology, Medicine, Pathology, Anatomy, Biochemistry
- MeSH
- cartilage, articular, chondrocytes, animals, cattle, humans, mice, arthritis, experimental, osteoarthritis, isothiocyanates, sulfoxides, matrix metalloproteinases, nf-kappa b, signal transduction, nf-e2-related factor 2
11 autores
- Rose K. Davidson🇬🇧University of East Anglia
- Orla J. Jupp🇬🇧University of East Anglia
- Rachel de Ferrars🇬🇧University of East Anglia
- Colin D. Kay🇬🇧University of East Anglia
- Kirsty L. Culley🇬🇧University of East Anglia
- Rosemary Norton🇬🇧University of East Anglia
- Clare Driscoll🇬🇧University of Oxford; British Society for Rheumatology
- Tonia L. Vincent🇬🇧University of Oxford; British Society for Rheumatology
- Simon Donell🇬🇧Norfolk and Norwich University Hospital
- Yongping Bao🇬🇧University of East Anglia
- Ian M. Clark🇬🇧 · autor de correspondenciaUniversity of East Anglia
Resumen
El texto original del estudio, en el idioma en que se publicó.
Objective
Sulforaphane (SFN) has been reported to regulate signaling pathways relevant to chronic diseases. The aim of this study was to investigate the impact of SFN treatment on signaling pathways in chondrocytes and to determine whether sulforaphane could block cartilage destruction in osteoarthritis.
Methods
Gene expression, histone acetylation, and signaling of the transcription factors NF-E2-related factor 2 (Nrf2) and NF-κB were examined in vitro. The bovine nasal cartilage explant model and the destabilization of the medial meniscus (DMM) model of osteoarthritis in the mouse were used to assess chondroprotection at the tissue and whole-animal levels.
Results
SFN inhibited cytokine-induced metalloproteinase expression in primary human articular chondrocytes and in fibroblast-like synovial cells. SFN acted independently of Nrf2 and histone deacetylase activity to regulate metalloproteinase expression in human articular chondrocytes but did mediate prolonged activation of JNK and p38 MAPK. SFN attenuated NF-κB signaling at least through inhibition of DNA binding in human articular chondrocytes, with decreased expression of several NF-κB-dependent genes. Compared with cytokines alone, SFN (10 μM) abrogated cytokine-induced destruction of bovine nasal cartilage at both the proteoglycan and collagen breakdown levels. An SFN-rich diet (3 μmoles/day SFN versus control chow) decreased the arthritis score in the DMM model of osteoarthritis in the mouse, with a concurrent block of early DMM-induced gene expression changes.
Conclusion
SFN inhibits the expression of key metalloproteinases implicated in osteoarthritis, independently of Nrf2, and blocks inflammation at the level of NF-κB to protect against cartilage destruction in vitro and in vivo.
Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial (CC BY).
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