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

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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.

Metabolic analysis of osteoarthritis subchondral bone

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Acknowledgments

This study was funded by National Natural Science Foundation of China (no. 89011060). The authors sincerely thank the subjects who participated in the study. The authors are also acknowledged for the sample collection at The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

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    Authors and Affiliations

    1. Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China

      Gang Yang, Hua Zhang, Weiwen Zhu, Kaiming Xu, Zhongwei Xu & Jian Zhang

    2. Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China

      Tingmei Chen & Shijia Ding

    3. Traditional Chinese Medicine Institute of Pharmaceutical Chemistry, Chongqing Institute of Traditional Chinese Medicine (TCM), Chongqing, 400065, China

      Yanlei Guo

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    1. Gang Yang
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    Correspondence to Jian Zhang.

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    All the authors declare that they have no conflict of interest. The experiment designed for this study involved subchondral bone from 42 patients with primary osteoarthritis. The experiment was approved by the ethics committee of Chongqing Medical University. Written informed consent was obtained from each individual participant.

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    Gang Yang and Hua Zhang contributed equally to this work.

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    Yang, G., Zhang, H., Chen, T. et al. Metabolic analysis of osteoarthritis subchondral bone based on UPLC/Q-TOF-MS. Anal Bioanal Chem 408, 4275–4286 (2016). https://doi.org/10.1007/s00216-016-9524-x

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