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
Yu  ZhangYu Zhang1Xiaochao  HuXiaochao Hu2Feng  ChenFeng Chen3Tongtong  LiuTongtong Liu2Ping  CaiPing Cai2Shijia  LiuShijia Liu2*Luning  SunLuning Sun2
  • 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

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

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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