Metabolic Analysis Of Osteoarthritis Sclerotic Subchondral Bone Based On UPLC/Q-TOF-MS

Objective: In this study, we apply the method of metabolomics to analyse the metabolomic profiling of subchondral bone in osteoarthritis of knee joint based on UPLC/Q-TOF-MS(ultra performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry), with the aim to look for the abnormal metabolites and metabolic pathways associated with this disease, and to explore the molecular mechanism of the sclerosis of subchondral bone in osteoarthritis.Methods: Based on the UPLC/Q-TOF-MS combined with the principal components analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA), the metabonome difference was analyzed between the sclerotic subchondral bone and non-sclerotic subchondral bone from 42 patients with primary knee osteoarthritis. T-test was applied to evaluate the significant differences. The different metabolites were identified to perform the metabolic pathway analysis, with the purpose to explore the abnormal metabolic pathways closely related to diseases, and thus explain the pathological molecular mechanisms of disease.Results: The metabolomic profiles of the experiment group and the control group were significantly different from each other. Sixty-eight metabolites were found significantly changed in the sclerotic subchondral bone in osteoarthritis(P<0.05). Alternations in taurine and hypotaurine metabolism, beta-Alanine metabolism, Phenylalanine metabolism, Tyrosine metabolism, Lysine degradation, Pyrimidine metabolism, Purine metabolism and Sphingolipid metabolism were also found to be related to osteoarthritis. In which, taurine and hypotaurine metabolism, and beta-Alanine metabolism were identified to be the most relevant to the sclerosis of subchondral bone in osteoarthritis. Taurine, L-carnitine and Glycerophospholipids played a vital regulation role in the pathology process of sclerotic subchondral bone. In addition, beta-Alanine and L-carnitine might be related to the increase of energy consumption.Conclusions: Based on the UPLC/Q-TOF-MS combined with multivariate statistical analysis, the metabolomic profiles could be distinguish between the sclerotic subchondral bone and non-sclerotic subchondral bone in osteoarthritis. The most disease-related abnormal metabolic molecules and pathways were found out. It provides a new pathway to study the molecular mechanism of sclerotic subchondral bone in osteoarthritis.