title: Exercise-driven metabolic pathways in healthy cartilage.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: 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.
authors.forename: A D
authors.initials: AD
authors.lastname: Blazek
authors.affiliation: Department of Bioengineering, University of California Riverside, Riverside, CA 92521, USA. Electronic address: jnam@engr.ucr.edu.
authors.forename: J
authors.initials: J
authors.lastname: Nam
authors.affiliation: Division of Biosciences, The Ohio State University (OSU) College of Dentistry, Columbus, OH 43210, USA. Electronic address: rohang614@gmail.com.
authors.forename: R
authors.initials: R
authors.lastname: Gupta
authors.affiliation: Division of Biosciences, The Ohio State University (OSU) College of Dentistry, Columbus, OH 43210, USA. Electronic address: meera.p07@gmail.com.
authors.forename: M
authors.initials: M
authors.lastname: Pradhan
authors.affiliation: Division of Biosciences, The Ohio State University (OSU) College of Dentistry, Columbus, OH 43210, USA. Electronic address: priyangi@pro-lab.com.
authors.forename: P
authors.initials: P
authors.lastname: Perera
authors.affiliation: 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.
authors.forename: N L
authors.initials: NL
authors.lastname: Weisleder
authors.affiliation: Sports Medicine Research, Department of Orthopedic Surgery, The Mayo Clinic, Rochester, MN 55905, USA. Electronic address: Hewett.Timothy@mayo.edu.
authors.forename: T E
authors.initials: TE
authors.lastname: Hewett
authors.affiliation: 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.
authors.forename: A M
authors.initials: AM
authors.lastname: Chaudhari
authors.affiliation: Department of Physiology and Cell Biology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA. Electronic address: Beth.Lee@osumc.edu.
authors.forename: B S
authors.initials: BS
authors.lastname: Lee
authors.affiliation: Division of Periodontics, The Ohio State University College of Dentistry, Columbus, OH 43210, USA. Electronic address: leblebicioglu.1@osu.edu.
authors.forename: B
authors.initials: B
authors.lastname: Leblebicioglu
authors.affiliation: Departments of Rehabilitation Sciences and Physiology, University of Kentucky, Lexington, KY 40536, USA. Electronic address: tim.butterfield@uky.edu.
authors.forename: T A
authors.initials: TA
authors.lastname: Butterfield
authors.affiliation: 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.
authors.forename: S
authors.initials: S
authors.lastname: Agarwal
mesh_terms: D000818:Animals; D002356:Cartilage; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053858:Metabolic Networks and Pathways; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D059467:Transcriptome
keywords: Cartilage; Exercise; Gene expression; Metabolic pathways; Osteoarthritis