Paula-Dene C. Nesbeth , Thomas R. Ziegler , Ashish Kumar Tripathi , Sadaf Dabeer , Daiana Weiss , Li Hao , Matthew R. Smith , Dean P. Jones , Kristal M. Maner-Smith , Chia-Ling Tu , Wenhan Chang , M. Neale Weitzmann , Jessica A. Alvarez
{"title":"亚油酸阻碍早期成骨细胞分化并损害体外氧化磷酸化","authors":"Paula-Dene C. Nesbeth , Thomas R. Ziegler , Ashish Kumar Tripathi , Sadaf Dabeer , Daiana Weiss , Li Hao , Matthew R. Smith , Dean P. Jones , Kristal M. Maner-Smith , Chia-Ling Tu , Wenhan Chang , M. Neale Weitzmann , Jessica A. Alvarez","doi":"10.1016/j.plefa.2024.102617","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>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.</p></div><div><h3>Methods</h3><p>The effect of LNA on osteoblast differentiation, cellular bioenergetics, and production of oxidized PUFA metabolites <em>in vitro</em>, was studied using primary mouse bone marrow stromal cells (BMSC) and MC3T3-E1 osteoblast precursors.</p></div><div><h3>Results</h3><p>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 <em>Runx2</em> and <em>Osterix</em>, 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.</p></div><div><h3>Conclusion</h3><p>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.</p></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":null,"pages":null},"PeriodicalIF":3.0000,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Linoleic acid blunts early osteoblast differentiation and impairs oxidative phosphorylation in vitro\",\"authors\":\"Paula-Dene C. Nesbeth , Thomas R. Ziegler , Ashish Kumar Tripathi , Sadaf Dabeer , Daiana Weiss , Li Hao , Matthew R. Smith , Dean P. Jones , Kristal M. Maner-Smith , Chia-Ling Tu , Wenhan Chang , M. Neale Weitzmann , Jessica A. Alvarez\",\"doi\":\"10.1016/j.plefa.2024.102617\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>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.</p></div><div><h3>Methods</h3><p>The effect of LNA on osteoblast differentiation, cellular bioenergetics, and production of oxidized PUFA metabolites <em>in vitro</em>, was studied using primary mouse bone marrow stromal cells (BMSC) and MC3T3-E1 osteoblast precursors.</p></div><div><h3>Results</h3><p>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 <em>Runx2</em> and <em>Osterix</em>, 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.</p></div><div><h3>Conclusion</h3><p>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.</p></div>\",\"PeriodicalId\":94179,\"journal\":{\"name\":\"Prostaglandins, leukotrienes, and essential fatty acids\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.0000,\"publicationDate\":\"2024-02-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Prostaglandins, leukotrienes, and essential fatty acids\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0952327824000115\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Prostaglandins, leukotrienes, and essential fatty acids","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0952327824000115","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Linoleic acid blunts early osteoblast differentiation and impairs oxidative phosphorylation in vitro
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
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
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
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.