Diagnostic biomarker panels of osteoarthritis: UPLC-QToF/MS-based serum metabolic profiling

Abstract

Osteoarthritis (OA) is the most common joint disease in the world, characterized by pain and loss of joint function, which has led to a serious reduction in the quality of patients’ lives. In this work, ultrahigh performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-QToF/MS) in conjunction with multivariate pattern recognition methods and an univariate statistical analysis scheme were applied to explore the serum metabolic signatures within OA group (n = 31), HC (healthy controls) group (n = 57) and non-OA group (n = 19) for early diagnosis and differential diagnosis of OA. Based on logistic regression analysis and receiver operating characteristic (ROC) curve analysis, seven metabolites, including phosphatidylcholine (18:0/22:6), p-cresol sulfate and so on, were identified as critical metabolites for the diagnosis of OA and HC and yielded an area under the curve (AUC) of 0.978. The other panel of unknown m/z 239.091, phosphatidylcholine (18:0/18:0) and phenylalanine were found to distinguish OA from non-OA and achieved an AUC of 0.888. These potential biomarkers are mainly involved in lipid metabolism, glucose metabolism and amino acid metabolism. It is expected to reveal new insight into OA pathogenesis from changed metabolic pathways.

Changes in the Serum Metabolome in an Inflammatory Model of Osteoarthritis in Rats

“…Lipid molecules were found at T0 vs T28 and T0 vs T84. These possible biomarkers were related to the findings of several studies, where there is an alteration of lipid metabolism associated with OA, due to its pro-inflammatory properties [16][17][18]35,36]. On the other hand, although in synovial fluid, Kosinska et al in several studies detect alterations at the level of phospholipids and sphingolipids at different stages of the disease [37][38][39], thus, understanding the relationship between OA and lipid molecules analysis may be helpfull in future treatments [8].…”

“…For this reason, it has become an ideal method for the identification of OA biomarkers in a variety of biological samples. Different studies have reported several metabolites and metabolic pathways that can be altered in OA, such as amino acid metabolism, fatty acid and lipids metabolism, phospholipids, arginine, phosphatidylcholine, L-tryptophan, tyrosine, carnitine, and arachidonic acid [1,2,4,9,[14][15][16][17][18][19].…”

Changes in the Serum Metabolome in an Inflammatory Model of Osteoarthritis in Rats

“…Lipid molecules were found at T0 vs. T28 and T0 vs. T84. These possible biomarkers were related to the findings of several studies, where there is an alteration of lipid metabolism associated with OA due to its pro-inflammatory properties [22][23][24]39,40]. Kosinska et al detected alterations at the level of phospholipids and sphingolipids at different stages of the disease in synovial fluid [41][42][43].…”

“…Phospholipids are molecules associated with inflammation and increased cartilage damage at the synovial fluid level and may be associated with the pathogenesis of OA [ 41 ]. The glycerophospholipids form the essential lipid bilayer of all biological membranes, and changes in glycerophospholipid concentrations and composition are associated with OA development, as shown in a multitude of studies [ 4 , 22 , 24 , 40 , 50 ]. Therefore, changes in the concentration of lipid molecules, more specifically glycerophospholipids, may indicate a risk of OA.…”

“…For this reason, it has become an ideal method for the identification of OA biomarkers in a variety of biological samples. Different studies have reported several metabolites and metabolic pathways that can be altered in OA, such as amino acid metabolism, fatty acid and lipid metabolism, phospholipids, arginine, phosphatidylcholine, L-tryptophan, tyrosine, carnitine, and arachidonic acid [ 1 , 2 , 4 , 10 , 20 , 21 , 22 , 23 , 24 , 25 ]. In order to identify biomarkers, one must go to the metabolic pathways that affect amino acid metabolism.…”