title: Metabolic profiling of synovial fluid in a unilateral ovine model of anterior cruciate ligament reconstruction of the knee suggests biomarkers for early osteoarthritis.
abstract: Joint injuries and subsequent osteoarthritis (OA) are the leading causes of chronic joint disease. In this work, we explore the possibility of applying magnetic resonance spectroscopy-based metabolomics to detect host responses to an anterior cruciate ligament (ACL) reconstruction injury in synovial fluid in an ovine model. Using multivariate statistical analysis, we were able to distinguish post-injury joint samples (ACL and sham surgery) from the uninjured control samples, and as well the ACL surgical samples from sham surgery. In all samples there were 65 metabolites quantified, of which six could be suggested as biomarkers for early post-injury degenerative changes in the knee joints: isobutyrate, glucose, hydroxyproline, asparagine, serine, and uridine. Our results raise a cautionary note indicating that surgical interventions into the knee can result in metabolic alterations that need to be distinguished from those caused by the early onset of OA. Our findings illustrate the potential application of metabolomics as a diagnostic and prognostic tool for detection of injuries to the knee joint. The ability to detect a unique pattern of metabolic changes in the synovial fluid of sheep offers the possibility of extending the approach to precision medicine protocols in patient populations in the future.
authors.affiliation: Bio-NMR Centre, Department of Biological Sciences, University of Calgary, Calgary, Alberta, Canada, T2N 1N4.
authors.forename: Beata
authors.initials: B
authors.lastname: Mickiewicz
authors.forename: Bryan J
authors.initials: BJ
authors.lastname: Heard
authors.forename: Johnny K
authors.initials: JK
authors.lastname: Chau
authors.forename: May
authors.initials: M
authors.lastname: Chung
authors.forename: David A
authors.initials: DA
authors.lastname: Hart
authors.forename: Nigel G
authors.initials: NG
authors.lastname: Shrive
authors.forename: Cyril B
authors.initials: CB
authors.lastname: Frank
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Vogel
mesh_terms: D000818:Animals; D059549:Anterior Cruciate Ligament Reconstruction; D001216:Asparagine / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005947:Glucose / Q000378:metabolism; D006909:Hydroxyproline / Q000378:metabolism; D058610:Isobutyrates / Q000378:metabolism; D007719:Knee Joint / Q000601:surgery*; D009682:Magnetic Resonance Spectroscopy; D055442:Metabolome; D020370:Osteoarthritis, Knee / Q000175:diagnosis* / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D012756:Sheep; D013582:Synovial Fluid / Q000378:metabolism*; D014529:Uridine / Q000378:metabolism
chemical_list: D015415:Biomarkers; D058610:Isobutyrates; D012694:Serine; D001216:Asparagine; D005947:Glucose; D006909:Hydroxyproline; D014529:Uridine
keywords: 1H nuclear magnetic resonance spectroscopy; knee injury; metabolomics; osteoarthritis; synovial fluid