Exercise-driven metabolic pathways in healthy cartilage

A. D. Blazek, J. Nam, R. Gupta, M. Pradhan, P. Perera, N. L. Weisleder, T. E. Hewett, A. M. Chaudhari, B. S. Lee, B. Leblebicioglu, T. A. Butterfield, S. Agarwal

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


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.

Original languageEnglish
Pages (from-to)1210-1222
Number of pages13
JournalOsteoarthritis and Cartilage
Issue number7
StatePublished - Jul 1 2016

Bibliographical note

Funding Information:
The funding sources were: National Institutes of Health , Bethesda, MD. Grant numbers AR048781 (S.A.), DE015399 (S.A.), AR063084 (N.W.), 32DEO14320 (J.N.) University of California , Riverside Initial Complement Funds (J.N.), Ohio State University Physiology and Cell Biology , Margaret T. Nishikawara Merit Scholarship Fund (A.D.B.). None of the study sponsors took part in the study design, collection, analysis and interpretation of data, writing of the manuscript, or in the decision of submitting the manuscript for publication.

Publisher Copyright:
© 2016 Osteoarthritis Research Society International.


  • Cartilage
  • Exercise
  • Gene expression
  • Metabolic pathways
  • Osteoarthritis

ASJC Scopus subject areas

  • Rheumatology
  • Biomedical Engineering
  • Orthopedics and Sports Medicine


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