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

doi:10.1016/j.joca.2016.02.004

Exercise-driven metabolic pathways in healthy cartilage

Osteoarthritis Cartilage. 2016 Jul;24(7):1210-22. doi: 10.1016/j.joca.2016.02.004. Epub 2016 Feb 27.

Authors

A D Blazek¹, J Nam², R Gupta³, M Pradhan⁴, P Perera⁵, N L Weisleder⁶, T E Hewett⁷, A M Chaudhari⁸, B S Lee⁹, B Leblebicioglu¹⁰, T A Butterfield¹¹, S Agarwal¹²

Affiliations

¹ Division of Biosciences, The Ohio State University (OSU) College of Dentistry, Columbus, OH 43210, USA; Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA. Electronic address: Blazek.16@osu.edu.
² Department of Bioengineering, University of California Riverside, Riverside, CA 92521, USA. Electronic address: jnam@engr.ucr.edu.
³ Division of Biosciences, The Ohio State University (OSU) College of Dentistry, Columbus, OH 43210, USA. Electronic address: rohang614@gmail.com.
⁴ Division of Biosciences, The Ohio State University (OSU) College of Dentistry, Columbus, OH 43210, USA. Electronic address: meera.p07@gmail.com.
⁵ Division of Biosciences, The Ohio State University (OSU) College of Dentistry, Columbus, OH 43210, USA. Electronic address: priyangi@pro-lab.com.
⁶ Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA; Department of Physiology and Cell Biology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA. Electronic address: Noah.Weisleder@osumc.edu.
⁷ Sports Medicine Research, Department of Orthopedic Surgery, The Mayo Clinic, Rochester, MN 55905, USA. Electronic address: Hewett.Timothy@mayo.edu.
⁸ Department of Physical Therapy, The Ohio State University School of Health and Rehabilitation Sciences, Columbus, OH 43210, USA; Department of Orthopedics, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA. Electronic address: chaudhari.2@osu.edu.
⁹ Department of Physiology and Cell Biology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA. Electronic address: Beth.Lee@osumc.edu.
¹⁰ Division of Periodontics, The Ohio State University College of Dentistry, Columbus, OH 43210, USA. Electronic address: leblebicioglu.1@osu.edu.
¹¹ Departments of Rehabilitation Sciences and Physiology, University of Kentucky, Lexington, KY 40536, USA. Electronic address: tim.butterfield@uky.edu.
¹² Division of Biosciences, The Ohio State University (OSU) College of Dentistry, Columbus, OH 43210, USA; Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA; Department of Orthopedics, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA. Electronic address: agarwal.61@osu.edu.

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.

Keywords: Cartilage; Exercise; Gene expression; Metabolic pathways; Osteoarthritis.

MeSH terms

Animals
Cartilage
Female
Gene Expression Profiling
Gene Expression Regulation
Metabolic Networks and Pathways*
Oligonucleotide Array Sequence Analysis
Rats
Rats, Sprague-Dawley
Transcriptome

Abstract

MeSH terms

Grants and funding