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ORIGINAL RESEARCH article

Front. Endocrinol.
Sec. Bone Research
Volume 15 - 2024 | doi: 10.3389/fendo.2024.1418932

Metabolomics Study of Osteopetrosis Caused by CLCN7 Mutation Reveals Novel Pathway and Potential Biomarkers

Provisionally accepted
Xi Chen Xi Chen 1Ziyuan Wang Ziyuan Wang 1Wenzhen Fu Wenzhen Fu 1Zhe Wei Zhe Wei 1Jie Mei Gu Jie Mei Gu 1Chun Wang Chun Wang 1ZhenLin Zhang ZhenLin Zhang 1*Xiangtian Yu Xiangtian Yu 2*Weiwei Hu Weiwei Hu 1*
  • 1 Shanghai Clinical Research Center of Bone Diseases，Department of Osteoporosis and Bone Diseases，Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
  • 2 Clinical Research Center, Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China

The final, formatted version of the article will be published soon.

    CLCN7 mutation caused abnormal osteoclasts, resulting in osteopetrosis. Depending on the type of mutation, CLCN7 mutations can lead to severe or relatively benign forms of osteopetrosis. However, the serum metabolic alterations in osteopetrosis caused by CLCN7 mutation are still unknown. We aimed to investigate the differences in the metabolome of osteopetrosis patients caused by CLCN7 mutation versus healthy controls (HC), uncovering potential subtype diagnosis biomarkers. 19 osteopetrosis patients caused by CLCN7 mutation and 19 HC were recruited for liquid chromatography-tandem mass spectrometry analysis. Three metabolic pathways were significantly enriched, including glycerophospholipid metabolism (P=0.036948), arachidonic acid metabolism (P=0.0058585) and linoleic acid metabolism (P=0.032035). Ten differential expressed metabolites were located in these three pathways and classified ability with areas under the curve over 0.7 in receiver operating characteristic analysis, suggesting a certain accuracy for being the potential biological markers. Especially, we found that the proteins in glycerophospholipid metabolism were predicted to interact with ClC-7 and further verified that the expression of coding genes were significantly up-regulated in myeloid cell specific Clcn7 G763R mutant mouse. This study provides data on serum metabolomics in osteopetrosis caused by CLCN7 mutation and provides new potential metabolic markers and pathways for diagnosis and pathogenesis of osteopetrosis.

    Keywords: Osteopetrosis, CLCN7 mutation, Metabolomics, liquid chromatography-tandem mass spectrometry, glycerophospholipid metabolism

    Received: 17 Apr 2024; Accepted: 13 May 2024.

    Copyright: © 2024 Chen, Wang, Fu, Wei, Gu, Wang, Zhang, Yu and Hu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    ZhenLin Zhang, Shanghai Clinical Research Center of Bone Diseases，Department of Osteoporosis and Bone Diseases，Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
    Xiangtian Yu, Clinical Research Center, Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
    Weiwei Hu, Shanghai Clinical Research Center of Bone Diseases，Department of Osteoporosis and Bone Diseases，Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China

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