ORIGINAL RESEARCH article
Front. Mol. Biosci.
Sec. Metabolomics
Volume 12 - 2025 | doi: 10.3389/fmolb.2025.1554936
Clinical metabolomics reveals potential diagnostic biomarkers in serum samples from patients with generalized ligamentous laxity
Provisionally accepted- 1Nanjing University of Chinese Medicine, Nanjing, China
- 2Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China
- 3School of Life Science and Technology, China Pharmaceutical University, Nanjing, Jiangsu Province, China
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Objectives: Discovering the potential metabolic alterations underlying generalized ligamentous laxity (GLL) is crucial for identifying new therapeutic targets and improving patient prognosis. Serum metabolites could mirror systemic and local alterations and help understand the metabolic features of GLL. The present work aimed to determine serum biomarkers for GLL diagnosis and to unveil metabolic pathways linked to GLL. Design: Prospective, observational cohort study. Methods: In this study, serum sample collection was conducted from 65 GLL and 35 healthy control (HC) cases. The obtained specimens were assessed by ultraperformance liquid chromatography high-resolution mass spectrometry (UPLC-HRMS). Orthogonal partial least squares-discriminant analysis (OPLS-DA), random forest (RF), binary logistic regression (BLR) and receiver operating characteristic (ROC) analyses were applied to screen and validate biomarkers.Results: Totally 24 small-molecules were considered differentially expressed metabolites. Of these, hexadecanamide was found to be a specific biomarker for differential diagnosis of GLL, with an area under the ROC curve (AUC) of 0.907.Additionally, the -linolenic acid and linoleic acid metabolism had the most substantial alteration among various pathways in GLL cases. The altered pathway of α-linolenic acid and linoleic acid metabolism affected bone mineral density and bone metabolism in GLL patients, leading to enhanced inflammation or fracture of the bone and joints.Joint inflammation and dislocation led to systemic ligament relaxation, which induced and aggravated musculoskeletal injury.Through identification of serum biomarkers and analysis of metabolic pathways, the current study provided novel insights into GLL pathogenesis.
Keywords: generalized ligamentous laxity, anti-inflammatory, Metabolomics, Osteoarthritis, biomarkers
Received: 19 Jan 2025; Accepted: 19 May 2025.
Copyright: © 2025 Zhang, Hu, Chen, Liu, Cai, Liu and Sun. 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: Shijia Liu, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China
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