Identifying chondroprotective diet-derived bioactives and investigating their synergism

Davidson, Rose K. ORCID: https://orcid.org/0000-0002-6624-4011, Green, Jonathan, Gardner, Sarah, Bao, Yongping ORCID: https://orcid.org/0000-0002-6425-0370, Cassidy, Aedin and Clark, Ian M. (2018) Identifying chondroprotective diet-derived bioactives and investigating their synergism. Scientific Reports, 8. ISSN 2045-2322

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Abstract

Osteoarthritis (OA) is a multifactorial disease and nutrition is a modifiable factor that may contribute to disease onset or progression. A detailed understanding of mechanisms through which diet-derived bioactive molecules function and interact in OA is needed. We profiled 96 diet-derived, mainly plant-based bioactives using an in vitro model in chondrocytes, selecting four candidates for further study. We aimed to determine synergistic interactions between bioactives that affected the expression of key genes in OA. Selected bioactives, sulforaphane, apigenin, isoliquiritigenin and luteolin, inhibited one or more interleukin-1-induced metalloproteinases implicated in OA (MMP1, MMP13, ADAMTS4, ADAMTS5). Isoliquiritigenin and luteolin showed reactive oxygen species scavenging activity in chondrocytes whereas sulforaphane had no effect and apigenin showed only a weak trend. Sulforaphane inhibited the IL-1/NFκB and Wnt3a/TCF/Lef pathways and increased TGFβ/Smad2/3 and BMP6/Smad1/5/8 signalling. Apigenin showed potent inhibition of the IL-1/NFκB and TGFβ/Smad2/3 pathways, whereas luteolin showed only weak inhibition of the IL-1/NFκB pathway. All four bioactives inhibited cytokine-induced aggrecan loss from cartilage tissue explants. The combination of sulforaphane and isoliquiritigenin was synergistic for inhibiting MMP13 gene expression in chondrocytes. We conclude that dietary-derived bioactives may be important modulators of cartilage homeostasis and synergistic relationships between bioactives may have an anti-inflammatory and chondroprotective role.

Item Type:	Article
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School Faculty of Science > School of Biological Sciences Faculty of Science
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Groups > Cancer Studies Faculty of Medicine and Health Sciences > Research Groups > Cardiovascular and Metabolic Health Faculty of Medicine and Health Sciences > Research Groups > Nutrition and Preventive Medicine Faculty of Medicine and Health Sciences > Research Groups > Musculoskeletal Medicine Faculty of Medicine and Health Sciences > Research Centres > Lifespan Health Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health
Depositing User:	LivePure Connector
Date Deposited:	07 Nov 2018 11:30
Last Modified:	13 Nov 2023 17:44
URI:	https://ueaeprints.uea.ac.uk/id/eprint/68794
DOI:	10.1038/s41598-018-35455-8

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