Metabolomic signature and molecular profile of normal and degenerated human intervertebral disc cells

Fecha de publicación: 01/10/2023 Fecha Ahead of Print: 01/09/2023

Autores de INCLIVA

Vera Lucía Gomes Francisco

Autor
Patrice Gomes Marques

Autor
Maria Jesus Sanz Ferrando

Autor
Jose Tomas Real Collado

Autor

Participantes ajenos a INCLIVA

Eldjoudi, Djedjiga Ait
Gonzalez-Rodriguez, Maria
Ruiz-Fernandez, Clara
Cordero-Barreal, Alfonso
Lago, Francisca
Pino, Jesus
Farrag, Yousof
Gualillo, Oreste

Grupos y Plataformas de I+D+i

Grupo de Investigación en Inflamación

Leading Researcher

Maria Jesus Sanz Ferrando
Grupo de Investigación sobre Riesgo Cardiometabólico y Diabetes

Leading Researcher

Sergio Martinez Hervas

Abstract

BACKGROUND CONTEXT: Intervertebral disc degeneration (IVDD) is an incurable, specific treatment-orphan disease with an increasing burden worldwide. Although great efforts have been made to develop new regenerative therapies, their clinical success is limited.PURPOSE: Characterize the metabolomic and gene expression changes underpinning human disc degeneration. This study also aimed to disclose new molecular targets for developing and optimizing novel biological approaches for IVDD.STUDY DESIGN: Intervertebral disc cells were obtained from IVDD patients undergoing circumferential arthrodesis surgery or from healthy subjects. Mimicking the harmful microenvironment of degenerated discs, cells isolated from the nucleus pulposus (NP) and annulus fibrosus (AF) were exposed to the proinflammatory cytokine IL-1b and the adipokine leptin. The metabolomic signature and molecular profile of human disc cells were unraveled for the first time.METHODS: The metabolomic and lipidomic profiles of IVDD and healthy disc cells were analyzed by high-performance liquid chromatography-mass spectrometry (UHPLC-MS). Gene expression was investigated by SYBR green-based quantitative real-time RT-PCR. Altered metabolites and gene expression were documented.RESULTS: Lipidomic analysis revealed decreased levels of triacylglycerols (TG), diacylglycerol (DG), fatty acids (FA), phosphatidylcholine (PC), lysophosphatidylinositols (LPI) and sphingomyelin (SM), and increased levels of bile acids (BA) and ceramides, likely promoting disc cell metabolism changing from glycolysis to fatty acid oxidation and following cell death. The gene expression profile of disc cells suggests LCN2 and LEAP2/GHRL as promising molecular therapeutic targets for disc degeneration and demonstrates the expression of genes related to inflammation (NOS2, COX2, IL-6, IL -8, IL-1 beta, and TNF-alpha) or encoding adipokines (PGRN, NAMPT, NUCB2, SERPINE2, and RARRES2), matrix metalloproteinases (MMP9 and MMP13), and vascular adhesion molecules (VCAM1).CONCLUSIONS: Altogether, the presented results disclose the NP and AF cell biology changes from healthy to degenerated discs, allowing the identification of promising molecular therapeutic targets for intervertebral disc degeneration.CLINICAL SIGNIFICANCE: Our results are relevant to improving current biological-based strategies aiming to repair IVD by restoring cellular lipid metabolites as well as adipokines homeostasis. Ultimately, our results will be valuable for successful, long-lasting relief of painful IVDD.(c) 2023 Elsevier Inc. All rights reserved.

Datos de la publicación

ISSN/ISSNe:: 1529-9430, 1878-1632
Tipo:: Article
Páginas:: 1549-1562
DOI:: 10.1016/j.spinee.2023.06.005
PubMed:: 37339697

Documentos

No hay documentos

Métricas

Filiaciones

Francisco, Vera:: Instituto de Investigación. Institute of Health Research INCLIVA and Endocrinology and Nutrition Service, University Clinic Hospital of Valencia, Calle Menéndez y Pelayo nº4, 46010 Valencia, Spain
Marques, Patrice:: Instituto de Investigación. University Clinic Hospital of Valencia and Department of Pharmacology, Faculty of Medicine and Odontology, Institute of Health Research INCLIVA, University of Valencia, Calle Menéndez y Pelayo, nº4, 46010 Valencia, Spain
Sanz, Maria Jesus:: CIBER. University Clinic Hospital of Valencia and Department of Pharmacology, Faculty of Medicine and Odontology, Institute of Health Research INCLIVA, University of Valencia, Calle Menéndez y Pelayo, nº4, 46010 Valencia, Spain. CIBERDEM-Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders, ISCIII, Av. Monforte de Lemos, 3-5, 28029 Madrid, Spain

Instituto de Investigación. University Clinic Hospital of Valencia and Department of Pharmacology, Faculty of Medicine and Odontology, Institute of Health Research INCLIVA, University of Valencia, Calle Menéndez y Pelayo, nº4, 46010 Valencia, Spain. CIBERDEM-Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders, ISCIII, Av. Monforte de Lemos, 3-5, 28029 Madrid, Spain
Real, Jose T:: CIBER. Institute of Health Research INCLIVA and Endocrinology and Nutrition Service, University Clinic Hospital of Valencia, Calle Menéndez y Pelayo nº4, 46010 Valencia, Spain. CIBERDEM-Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders, ISCIII, Av. Monforte de Lemos, 3-5, 28029 Madrid, Spain. Department of Medicine, Faculty of Medicine and Odontology, University of Valencia, Av. de Blasco Ibáñez nº15, 46010 Valencia, Spain

Instituto de Investigación. Institute of Health Research INCLIVA and Endocrinology and Nutrition Service, University Clinic Hospital of Valencia, Calle Menéndez y Pelayo nº4, 46010 Valencia, Spain. CIBERDEM-Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders, ISCIII, Av. Monforte de Lemos, 3-5, 28029 Madrid, Spain. Department of Medicine, Faculty of Medicine and Odontology, University of Valencia, Av. de Blasco Ibáñez nº15, 46010 Valencia, Spain

Keywords

Adipokines; Human; Inflammation; Intervertebral disc; Lipids; Metabolism; Therapy; Adipokines; Human; Inflammation; Intervertebral disc; Lipids; Metabolism; Therapy