Metabolic analysis of osteoarthritis subchondral bone based on UPLC/Q-TOF-MS

Abstract

Osteoarthritis (OA), one of the most widespread musculoskeletal joint diseases among the aged, is characterized by the progressive loss of articular cartilage and continuous changes in subchondral bone. The exact pathogenesis of osteoarthritis is not completely clear. In this work, ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF-MS) in combination with multivariate statistical analysis was applied to analyze the metabolic profiling of subchondral bone from 42 primary osteoarthritis patients. This paper described a modified two-step method for extracting the metabolites of subchondral bone from primary osteoarthritis patients. Finally, 68 metabolites were identified to be significantly changed in the sclerotic subchondral bone compared with the non-sclerotic subchondral bone. Taurine and hypotaurine metabolism and beta-alanine metabolism were probably relevant to the sclerosis of subchondral bone. Taurine, L-carnitine, and glycerophospholipids played a vital regulation role in the pathological process of sclerotic subchondral bone. In the sclerotic process, beta-alanine and L-carnitine might be related to the increase of energy consumption. In addition, our findings suggested that the intra-cellular environment of sclerotic subchondral bone might be more acidotic and hypoxic compared with the non-sclerotic subchondral bone. In conclusion, this study provided a new insight into the pathogenesis of subchondral bone sclerosis. Our results indicated that metabolomics could serve as a promising approach for elucidating the pathogenesis of subchondral bone sclerosis in primary osteoarthritis. Graphical Abstract Metabolic analysis of osteoarthritis subchondral bone.

Keywords: Metabolic pathways; Metabolomics; Osteoarthritis; Subchondral bone; UPLC/Q-TOF-MS.