ORIGINAL RESEARCH article
Front. Physiol.
Sec. Cell Physiology
Volume 16 - 2025 | doi: 10.3389/fphys.2025.1641445
Metabolomic Profiling Reveals Novel Biomarkers and Therapeutic Targets in Legg-Calvé -Perthes Disease: A Comprehensive Analysis of Peripheral Blood and Endothelial Function
Provisionally accepted
- 1920th Hospital of People's Liberation Army Joint Logistic Support Force, Kunming, China
- 2Kunming Children's Hospital, Kunming, China
- 3Department of Orthopedic Surgery, The 920th Hospital of Joint Logistics Support Force, Kunming, China
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Legg-Calvé -Perthes Disease (LCPD), a childhood hip disorder of idiopathic femoral head avascular necrosis, has unclear pathophysiology, hindering therapeutic development. This study aimed to identify metabolic biomarkers and clarify the roles of peripheral inflammation and vascular dysfunction in LCPD. Peripheral blood from 36 LCPD patients and 6 controls underwent metabolomic profiling (LC-MS), with pathway analysis of differential metabolites. Protective effects of 3-ketoglucose and sanguinarine were validated in lipopolysaccharide (LPS)-induced inflamed human umbilical vein endothelial cells (HUVECs). Validation included RNA sequencing, measuring reactive oxygen species (ROS), pro-inflammatory cytokines, and cell signaling. Our metabolomic analysis identified 38 significantly altered metabolites in LCPD patients, notably upregulated 3-ketoglucose and sanguinarine, and downregulated 6-hydroxymelin and N-methyl-D-aspartate. These changes were associated with inflammatory and oxidative stress pathways. Significantly, both 3ketoglucose and sanguinarine attenuated LPS-induced endothelial cell inflammation by reducing ROS and pro-inflammatory cytokine levels, and modulating key signaling pathways including nuclear factor kappa B (NF-κB), endothelial nitric oxide synthase (eNOS), and vascular cell adhesion molecule 1 (VCAM-1). Crucially, in the animal model, both compounds ameliorated bone loss, reduced adipogenesis, and consistently modulated these key genes in vivo, confirming their therapeutic potential.This research provides the first comprehensive metabolomic fingerprint of LCPD, establishing a critical link between systemic metabolic changes, peripheral inflammation, and endothelial dysfunction. These findings offer a conceptual advance by identifying specific metabolites with protective actions as potential new diagnostic biomarkers and therapeutic targets for LCPD.
Keywords: Legg-Calvé -Perthes Disease, Metabolomics, Vascular Dysfunction, Inflammation, Endothelial Cells, 3-Ketoglucose, Sanguinarine
Received: 05 Jun 2025; Accepted: 11 Aug 2025.
Copyright: © 2025 Zi, Wang, Zhang, Lv, Wan, He, Hang and Xu. 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: Yongqing Xu, Department of Orthopedic Surgery, The 920th Hospital of Joint Logistics Support Force, Kunming, China
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