¹H NMR Spectroscopy of Serum Reveals Unique Metabolic Fingerprints Associated with Subtypes of Surgically Induced Osteoarthritis in Sheep

Abstract

Osteoarthritis (OA) is a highly prevalent joint disease. Its slow progressive nature and the correlation between pathological changes and clinical symptoms mean that OA is often well advanced by the time of diagnosis. In the absence of any specific pharmacological treatments, there is a pressing need to develop robust biomarkers for OA. We have adopted a nuclear magnetic resonance (NMR)-based metabolomic strategy to identify molecular responses to surgically induced OA in an animal model. Sheep underwent one of three types of surgical procedure (sham (control), meniscal destabilization, MD or anterior cruciate ligament transaction, ACLT), and for every animal a serum sample was collected both pre- and postoperatively, thus, affording two types of "control" data for comparison. 1D 1H NMR spectra were acquired from each sample at 800 MHz and the digitized spectral data were analyzed using principal components analysis and partial least-squares regression discriminant analysis. Our approach, combined with the study design, allowed us to separate the metabolic responses to surgical intervention from those associated with OA. We were able to identify dimethyl sulfone (DMSO2) as being increased in MD after 4 weeks, while ACLT-induced OA exhibited increased 3-methylhistidine and decreased branched chain amino acids (BCAAs). The findings are discussed in the context of interpretation of metabolomic results in studies of human disease, and the selection of appropriate "control" data sets.

Metabolic profiling of synovial fluid in a unilateral ovine model of anterior cruciate ligament reconstruction of the knee suggests biomarkers for early osteoarthritis

“…Our findings provide evidence that the metabolic profile detected in the SF is robust for identifying 2 weeks post‐injury joints as evidenced by the high account of variance (R2Y) and predictive ability (Q2) of the supervised PLS‐DA model. It has already been reported that knee surgery itself might induce very detectable metabolic changes . The lack of separation between the samples collected from idealized ACL reconstruction joints and sham‐surgical joints in the unsupervised PCA model confirms that the major source of variation in the dataset (surgical and non‐surgical samples taken together) can be related to the inflammation and very similar initial joint injury/damage in the first 2 weeks after the surgery.…”

Review of Soluble Biomarkers of Osteoarthritis: Lessons From Animal Models

“…77 In another study, synovial fluid of MMP-2 was detected 2 and 4 weeks postoperatively in a temporomandibular joint (TMJ) model of OA in sheep. 78 Moreover, MMP-2 activity correlated with initial articular cartilage destruction rather than with the progression of OA.…”

Methylsulfonylmethane: Applications and Safety of a Novel Dietary Supplement

“…In fact the protective effects of MSM can be seen as far back as 1991, when Murav’ev and colleagues described the decreased knee joint degeneration of arthritic mice [150]. Interestingly, endogenous serum MSM becomes elevated in sheep post-meniscal destabilization caused osteoarthritis [151]; however, the magnitude of this physiological response was not large enough to protect against cartilage erosion.…”