Dataset Information

Physical Activity Prevents Cartilage Degradation: A Metabolomics Study Pinpoints the Involvement of Vitamin B6.

ABSTRACT: Osteoarthritis (OA) is predominantly characterized by the progressive degradation of articular cartilage, the connective tissue produced by chondrocytes, due to an imbalance between anabolic and catabolic processes. In addition, physical activity (PA) is recognized as an important tool for counteracting OA. To evaluate PA effects on the chondrocyte lineage, we analyzed the expression of SOX9, COL2A1, and COMP in circulating progenitor cells following a half marathon (HM) performance. Therefore, we studied in-depth the involvement of metabolites affecting chondrocyte lineage, and we compared the metabolomic profile associated with PA by analyzing runners' sera before and after HM performance. Interestingly, this study highlighted that metabolites involved in vitamin B6 salvage, such as pyridoxal 5'-phosphate and pyridoxamine 5'-phosphate, were highly modulated. To evaluate the effects of vitamin B6 in cartilage cells, we treated differentiated mesenchymal stem cells and the SW1353 chondrosarcoma cell line with vitamin B6 in the presence of IL1?, the inflammatory cytokine involved in OA. Our study describes, for the first time, the modulation of the vitamin B6 salvage pathway following PA and suggests a protective role of PA in OA through modulation of this pathway.

SUBMITTER: Deiana M

PROVIDER: S-EPMC6912200 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Physical Activity Prevents Cartilage Degradation: A Metabolomics Study Pinpoints the Involvement of Vitamin B6.

Deiana Michela M Malerba Giovanni G Dalle Carbonare Luca L Cheri Samuele S Patuzzo Cristina C Tsenov Grygoriy G Moron Dalla Tor Lucas L Mori Antonio A Saviola Gianantonio G Zipeto Donato D Schena Federico F Mottes Monica M Valenti Maria Teresa MT

Cells 20191101 11

Osteoarthritis (OA) is predominantly characterized by the progressive degradation of articular cartilage, the connective tissue produced by chondrocytes, due to an imbalance between anabolic and catabolic processes. In addition, physical activity (PA) is recognized as an important tool for counteracting OA. To evaluate PA effects on the chondrocyte lineage, we analyzed the expression of SOX9, COL2A1, and COMP in circulating progenitor cells following a half marathon (HM) performance. Therefore, ...[more]

PMID: 31683926

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Project description:UnlabelledPhotorhabdus luminescens is a Gram-negative entomopathogenic bacterium which symbiotically associates with the entomopathogenic nematode Heterorhabditis bacteriophora P. luminescens is highly virulent to many insects and nonsymbiotic nematodes, including Caenorhabditis elegans To understand the virulence mechanisms of P. luminescens, we obtained virulence-deficient and -attenuated mutants against C. elegans through a transposon-mutagenized library. From the genetic screening, we identified the pdxB gene, encoding erythronate-4-phosphate dehydrogenase, as required for de novo vitamin B6 biosynthesis. Mutation in pdxB caused growth deficiency of P. luminescens in nutrient-poor medium, which was restored under nutrient-rich conditions or by supplementation with pyridoxal 5'-phosphate (PLP), an active form of vitamin B6 Supplementation with three other B6 vitamers (pyridoxal, pyridoxine, and pyridoxamine) also restored the growth of the pdxB mutant, suggesting the existence of a salvage pathway for vitamin B6 biosynthesis in P. luminescens Moreover, supplementation with PLP restored the virulence-deficient phenotype against C. elegans Combining these results with the fact that pdxB mutation also caused attenuation of insecticidal activity, we concluded that the production of appropriate amounts of vitamin B6 is critical for P. luminescens pathogenicity.ImportanceThe Gram-negative entomopathogenic bacterium Photorhabdus luminescens symbiotically associates with the entomopathogenic nematode Heterorhabditis bacteriophora P. luminescens is highly virulent to many insects and nonsymbiotic nematodes, including Caenorhabditis elegans We have obtained several virulence-deficient and -attenuated P. luminescens mutants against C. elegans through genetic screening. From the genetic analysis, we present the vitamin B6 biosynthetic pathways in P. luminescens that are important for its insecticidal activity. Mutation in pdxB, encoding erythronate-4-phosphate dehydrogenase and required for the de novo vitamin B6 biosynthesis pathway, caused virulence deficiency against C. elegans and growth deficiency of P. luminescens in nutrient-poor medium. Because such phenotypes were restored under nutrient-rich conditions or by supplementation with B6 vitamers, we showed the presence of the two vitamin B6 synthetic pathways (de novo and salvage) in P. luminescens and also showed that the ability to produce an appropriate amount of vitamin B6 is critical for P. luminescens pathogenicity.

Project description:BackgroundPhysical activity is associated with a variety of health benefits, but the biological mechanisms that explain these associations remain unclear. Metabolomics is a powerful tool to comprehensively evaluate global metabolic signature associated with physical activity and helps to pinpoint the pathways that mediate the health effects of physical activity. There has been limited research on metabolomics and habitual physical activity, and no metabolomics study has examined sedentary behaviour and physical activity of different intensities.MethodsIn a group of Chinese adults (N = 277), we used an untargeted approach to examine 328 plasma metabolites in relation to accelerometer-measured physical activity, including overall volume of physical activity (physical activity energy expenditure (PAEE) and duration of physically active time) and sedentary time, and measures related to different intensities of physical activity (moderate-to-vigorous activity (MVPA), light activity, average physical activity intensity).ResultsWe identified 11 metabolites that were associated with total activity, with a false discovery rate of 0.2 or lower. Notably, we observed generally lower levels of amino acids in the valine, leucine and isoleucine metabolism pathway and of carbohydrates in sugar metabolism among participants with higher activity levels. Moreover, we found that PAEE, time spent in light activity and duration of physically active time were associated with a similar metabolic pattern, whereas the metabolic signature associated with sedentary time mirrored this pattern. In contrast, average activity intensity and time spent in MVPA appeared to be associated with somewhat different metabolic patterns.ConclusionsOverall, the metabolomics patterns support a beneficial role of higher volume of physical activity in cardiometabolic health. Our findings identified candidate pathways and provide insight into the mechanisms underlying the health effects of physical activity.

Dataset Information

Physical Activity Prevents Cartilage Degradation: A Metabolomics Study Pinpoints the Involvement of Vitamin B6.

Publications

Physical Activity Prevents Cartilage Degradation: A Metabolomics Study Pinpoints the Involvement of Vitamin B6.

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