AUTHOR=Southan Jennifer , McHugh Emily , Walker Heather , Ismail Heba M. 

TITLE=Metabolic Signature of Articular Cartilage Following Mechanical Injury: An Integrated Transcriptomics and Metabolomics Analysis

JOURNAL=Frontiers in Molecular Biosciences

VOLUME=Volume 7 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2020.592905

DOI=10.3389/fmolb.2020.592905

ISSN=2296-889X

ABSTRACT=Mechanical injury to articular cartilage is a key risk factor in joint damage and predisposition to osteoarthritis. Integrative multi-omics approaches provide a valuable tool to understand the tissue behaviour in response to mechanical injury insult and help to identify key pathways linking injury to tissue damage. 
 
Global or untargeted metabolomics provides a comprehensive characterization of the metabolite content of biological samples. In this study, we aimed to identify the metabolic signature of cartilage tissue post injury. We employed an integrative analysis of transcriptomics and global metabolomics of murine epiphyseal hip cartilage before and after injury. Transcriptomics analysis showed a significant enrichment of gene sets involved in regulation of metabolic processes including carbon metabolism, biosynthesis of amino acids, and steroid biosynthesis. Integrative analysis of enriched genes with putatively identified metabolites features post injury showed a significant enrichment for carbohydrate metabolism (glycolysis, galactose, glycosylate metabolism and pentose phosphate pathway) and amino acids metabolism (Arginine biosynthesis, tyrosine, glycine, serine, threonine, Arginine and proline metabolism).  We then performed a cross analysis of global metabolomics profiles of murine and porcine ex-vivo cartilage injury models. The top commonly modulated metabolic pathways post injury included arginine and proline metabolism, arginine biosynthesis, glycolysis/ gluconeogenesis and vitamin B6 metabolic pathways.
 
These results highlight the significant modulation of metabolic responses following mechanical injury to articular cartilage. Further investigation of these pathways would provide new insights into the role of the early metabolic state of articular cartilage post injury in promoting tissue damage and its link to disease progression of osteoarthritis.