Title | Exercise-driven metabolic pathways in healthy cartilage. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Blazek AD, Nam J, Gupta R, Pradhan M, Perera P, Weisleder NL, Hewett TE, Chaudhari AM, Lee BS, Leblebicioglu B, Butterfield TA, Agarwal S |
Journal | Osteoarthritis Cartilage |
Volume | 24 |
Issue | 7 |
Pagination | 1210-22 |
Date Published | 2016 07 |
ISSN | 1522-9653 |
Keywords | Animals, Cartilage, Female, Gene Expression Profiling, Gene Expression Regulation, Metabolic Networks and Pathways, Oligonucleotide Array Sequence Analysis, Rats, Rats, Sprague-Dawley, Transcriptome |
Abstract | OBJECTIVE: Exercise is vital for maintaining cartilage integrity in healthy joints. Here we examined the exercise-driven transcriptional regulation of genes in healthy rat articular cartilage to dissect the metabolic pathways responsible for the potential benefits of exercise. METHODS: Transcriptome-wide gene expression in the articular cartilage of healthy Sprague-Dawley female rats exercised daily (low intensity treadmill walking) for 2, 5, or 15 days was compared to that of non-exercised rats, using Affymetrix GeneChip arrays. Database for Annotation, Visualization and Integrated Discovery (DAVID) was used for Gene Ontology (GO)-term enrichment and Functional Annotation analysis of differentially expressed genes (DEGs). Kyoto Encyclopedia of Genes and Genome (KEGG) pathway mapper was used to identify the metabolic pathways regulated by exercise. RESULTS: Microarray analysis revealed that exercise-induced 644 DEGs in healthy articular cartilage. The DAVID bioinformatics tool demonstrated high prevalence of functional annotation clusters with greater enrichment scores and GO-terms associated with extracellular matrix (ECM) biosynthesis/remodeling and inflammation/immune response. The KEGG database revealed that exercise regulates 147 metabolic pathways representing molecular interaction networks for Metabolism, Genetic Information Processing, Environmental Information Processing, Cellular Processes, Organismal Systems, and Diseases. These pathways collectively supported the complex regulation of the beneficial effects of exercise on the cartilage. CONCLUSIONS: Overall, the findings highlight that exercise is a robust transcriptional regulator of a wide array of metabolic pathways in healthy cartilage. The major actions of exercise involve ECM biosynthesis/cartilage strengthening and attenuation of inflammatory pathways to provide prophylaxis against onset of arthritic diseases in healthy cartilage. |
DOI | 10.1016/j.joca.2016.02.004 |
Alternate Journal | Osteoarthr. Cartil. |
PubMed ID | 26924420 |
PubMed Central ID | PMC4907806 |
Grant List | R01 AR048781 / AR / NIAMS NIH HHS / United States R01 AR063084 / AR / NIAMS NIH HHS / United States R01 AT000646 / AT / NCCIH NIH HHS / United States R01 DE015399 / DE / NIDCR NIH HHS / United States |