Linoleic acid blunts early osteoblast differentiation and impairs oxidative phosphorylation in vitro.

Bone Linoleic acid Osteoblast Oxidative phosphorylation Oxylipin Polyunsaturated fatty acids

Journal

Prostaglandins, leukotrienes, and essential fatty acids
ISSN: 1532-2823
Titre abrégé: Prostaglandins Leukot Essent Fatty Acids
Pays: Scotland
ID NLM: 8802730

Informations de publication

Date de publication:
09 May 2024
Historique:
received: 24 10 2023
revised: 17 04 2024
accepted: 08 05 2024
medline: 25 5 2024
pubmed: 25 5 2024
entrez: 24 5 2024
Statut: aheadofprint

Résumé

Linoleic acid (LNA), an essential polyunsaturated fatty acid (PUFA), plays a crucial role in cellular functions. However, excessive intake of LNA, characteristic of Western diets, can have detrimental effects on cells and organs. Human observational studies have shown an inverse relationship between plasma LNA concentrations and bone mineral density. The mechanism by which LNA impairs the skeleton is unclear, and there is a paucity of research on the effects of LNA on bone-forming osteoblasts. The effect of LNA on osteoblast differentiation, cellular bioenergetics, and production of oxidized PUFA metabolites in vitro, was studied using primary mouse bone marrow stromal cells (BMSC) and MC3T3-E1 osteoblast precursors. LNA treatment decreased alkaline phosphatase activity, an early marker of osteoblast differentiation, but had no effect on committed osteoblasts or on mineralization by differentiated osteoblasts. LNA suppressed osteoblast commitment by blunting the expression of Runx2 and Osterix, key transcription factors involved in osteoblast differentiation, and other key osteoblast-related factors involved in bone formation. LNA treatment was associated with increased production of oxidized LNA- and arachidonic acid-derived metabolites and blunted oxidative phosphorylation, resulting in decreased ATP production. Our results show that LNA inhibited early differentiation of osteoblasts and this inhibitory effect was associated with increased production of oxidized PUFA metabolites that likely impaired energy production via oxidative phosphorylation.

Sections du résumé

BACKGROUND BACKGROUND
Linoleic acid (LNA), an essential polyunsaturated fatty acid (PUFA), plays a crucial role in cellular functions. However, excessive intake of LNA, characteristic of Western diets, can have detrimental effects on cells and organs. Human observational studies have shown an inverse relationship between plasma LNA concentrations and bone mineral density. The mechanism by which LNA impairs the skeleton is unclear, and there is a paucity of research on the effects of LNA on bone-forming osteoblasts.
METHODS METHODS
The effect of LNA on osteoblast differentiation, cellular bioenergetics, and production of oxidized PUFA metabolites in vitro, was studied using primary mouse bone marrow stromal cells (BMSC) and MC3T3-E1 osteoblast precursors.
RESULTS RESULTS
LNA treatment decreased alkaline phosphatase activity, an early marker of osteoblast differentiation, but had no effect on committed osteoblasts or on mineralization by differentiated osteoblasts. LNA suppressed osteoblast commitment by blunting the expression of Runx2 and Osterix, key transcription factors involved in osteoblast differentiation, and other key osteoblast-related factors involved in bone formation. LNA treatment was associated with increased production of oxidized LNA- and arachidonic acid-derived metabolites and blunted oxidative phosphorylation, resulting in decreased ATP production.
CONCLUSION CONCLUSIONS
Our results show that LNA inhibited early differentiation of osteoblasts and this inhibitory effect was associated with increased production of oxidized PUFA metabolites that likely impaired energy production via oxidative phosphorylation.

Identifiants

DOI: 10.1016/j.plefa.2024.102617 PMID: 38788347
pubmed: 38788347
pii: S0952-3278(24)00011-5
doi: 10.1016/j.plefa.2024.102617
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

102617

Informations de copyright

Copyright © 2024. Published by Elsevier Ltd.

Déclaration de conflit d'intérêts

Declaration of competing interest The authors have no conflict of interest to disclose.

Auteurs

Paula-Dene C Nesbeth (PC)

Nutrition and Health Sciences Doctoral Program, Laney Graduate School, Emory University, Atlanta, GA, USA; Division of Endocrinology, Metabolism, and Lipids, Department of Medicine, School of Medicine, Emory University, Atlanta, GA, USA; Emory Center for Clinical and Molecular Nutrition, Emory University, Atlanta, GA, USA.

Thomas R Ziegler (TR)

Division of Endocrinology, Metabolism, and Lipids, Department of Medicine, School of Medicine, Emory University, Atlanta, GA, USA; Emory Center for Clinical and Molecular Nutrition, Emory University, Atlanta, GA, USA.

Ashish Kumar Tripathi (AK)

Division of Endocrinology, Metabolism, and Lipids, Department of Medicine, School of Medicine, Emory University, Atlanta, GA, USA.

Sadaf Dabeer (S)

Division of Endocrinology, Metabolism, and Lipids, Department of Medicine, School of Medicine, Emory University, Atlanta, GA, USA; Atlanta Department of Veterans Affairs Medical Center, Decatur, GA, USA.

Daiana Weiss (D)

Division of Endocrinology, Metabolism, and Lipids, Department of Medicine, School of Medicine, Emory University, Atlanta, GA, USA.

Li Hao (L)

Division of Endocrinology, Metabolism, and Lipids, Department of Medicine, School of Medicine, Emory University, Atlanta, GA, USA.

Matthew R Smith (MR)

Atlanta Department of Veterans Affairs Medical Center, Decatur, GA, USA; Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, School of Medicine, Emory University, Atlanta, GA, USA.

Dean P Jones (DP)

Emory Center for Clinical and Molecular Nutrition, Emory University, Atlanta, GA, USA; Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, School of Medicine, Emory University, Atlanta, GA, USA.

Kristal M Maner-Smith (KM)

Department of Biochemistry, Emory University, Atlanta, Georgia, USA.

Chia-Ling Tu (CL)

Endocrine Research Unit, San Francisco VA Healthcare System, University of California, San Francisco, CA, USA.

Wenhan Chang (W)

Endocrine Research Unit, San Francisco VA Healthcare System, University of California, San Francisco, CA, USA.

M Neale Weitzmann (MN)

Division of Endocrinology, Metabolism, and Lipids, Department of Medicine, School of Medicine, Emory University, Atlanta, GA, USA; Atlanta Department of Veterans Affairs Medical Center, Decatur, GA, USA.

Jessica A Alvarez (JA)

Division of Endocrinology, Metabolism, and Lipids, Department of Medicine, School of Medicine, Emory University, Atlanta, GA, USA; Emory Center for Clinical and Molecular Nutrition, Emory University, Atlanta, GA, USA. Electronic address: Jessica.Alvarez@emory.edu.

Classifications MeSH