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This study applies multimodal profiling—untargeted LC–MS lipidomics, Raman spectroscopy, FLIM, and structural imaging—to track CL remodeling in human adipose-derived stem cells. Lipidomics shows enrichment of highly unsaturated CL species and coordinated upregulation of CL biosynthetic/remodeling enzymes, linking CL metabolism to mitochondrial expansion, oxidative phosphorylation, matrix mineralization, and osteoblast maturation. The work identifies CL remodeling as a metabolic checkpoint and suggests targeted CL modulation as a potential strategy to enhance bone regeneration.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/cardiolipin-remodeling-as-a-regulatory-switch-in-osteogenesis-insights-from-multimodal-metabolic-imaging-and-molecular-profiling/447206/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/cardiolipin-remodeling-as-a-regulatory-switch-in-osteogenesis-insights-from-multimodal-metabolic-imaging-and-molecular-profiling/447206.png","ImageObject",300,407,{"name":92,"@type":93},"jay","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":24},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What question does this study address about cardiolipin in osteogenesis?","Question",{"text":112,"@type":113},"The study investigates how cardiolipin (CL) remodeling contributes to osteogenic differentiation, which has been poorly defined despite CL’s role in mitochondrial bioenergetics.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Which multimodal techniques were used to study CL remodeling during differentiation?",{"text":117,"@type":113},"It combines untargeted LC–MS lipidomics, Raman spectroscopy, fluorescence lifetime imaging microscopy (FLIM), and structural imaging to examine lipid changes and their spatial and metabolic links to differentiation.",{"name":119,"@type":110,"acceptedAnswer":120},"What metabolic shift was observed during osteogenic differentiation?",{"text":121,"@type":113},"FLIM data indicates a time-linked shift from glycolysis toward oxidative phosphorylation during differentiation, supported by structural and gene expression evidence.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},447206,1791163012,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":24,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},3985747858866,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","bioRxiv preprint doi: [https://doi.org/10.64898/2025.12.22.696122](https://doi.org/10.64898/2025.12.22.696122); this version posted December 23, 2025. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made  \navailable under aCC-BY-ND 4.0 International license.  \n1  \n2 Title  \n3 Cardiolipin Remodeling as a Regulatory Switch in Osteogenesis: Insights from Multimodal  \n4 Metabolic Imaging and Molecular Profiling 5  \n6 Authors  \n7 Maria Iftesum 1, Praveen Kumar Guttula 1, Kirti Agrawal 1, Subhrajyoti S Kundu 1, Sreyashi  \n8 Das2, Fabrizio Donnarumma3, Ram Devireddy 1, Manas Ranjan Gartia 1 *  \n9 Affiliations  \n10 1Department of Mechanical and Industrial Engineering, Louisiana State University, Baton  \n11 Rouge, LA 70803, USA.  \n12 2Department of Chemistry, University of Florida, Gainesville, FL 32611, USA.  \n13 3Mass Spectrometry Facility, Department of Chemistry, Louisiana State University, Baton  \n14 Rouge, LA 70803, USA.  \n15  \n16 *Address correspondence to: Manas Ranjan Gartia; [mgartia@lsu.edu](mgartia@lsu.edu)  \n17  \n18  \n19  \n20 ABSTRACT 21  \n22 Cardiolipin (CL), a mitochondria-specific phospholipid, plays a fundamental role in  \n23 respiratory chain organization and bioenergetic efficiency, yet its contribution to osteogenic  \n24 differentiation is poorly defined. Here, we used a multimodal approach integrating untargeted LC–  \n25 MS lipidomics, Raman spectroscopy, fluorescence lifetime imaging microscopy (FLIM), and  \n26 structural imaging to investigate CL remodeling during human adipose-derived stem cell  \n27 differentiation. Lipidomics revealed a selective enrichment of highly unsaturated CL species,  \n28 accompanied by transcriptional upregulation of the cardiolipin biosynthetic and remodeling  \n29 enzymes CDS1/2, PGS1, CRLS1, TAZ, and HADHA. Lipidomics also revealed a time-dependent  \n30 increase in membrane-associated lipids including phosphatidylcholine (PC), serine, and  \n31 phosphatidylinositol (PI) . These lipids were implicated in supporting mitochondrial membrane  \n32 expansion, oxidative phosphorylation, and signaling processes critical for osteoblast maturation.  \n33 Spatial imaging techniques confirmed cardiolipin accumulation and redistribution in differentiated  \n34 cells, while Raman-based direct classical least squares (DCLS) analysis provided label-free  \n35 mapping of lipid species. Gene Ontology (GO) enrichment and protein–protein interaction network  \n36 analysis further identified biological pathways related to bone remodeling, cardiolipin metabolism,  \n37 and osteoblast-specific signaling. Fluorescence Lifetime Imaging Microscopy (FLIM) data  \n38 revealed a metabolic shift from glycolysis to oxidative phosphorylation during differentiation,  \n39 supported by structural and gene expression evidence. These changes temporally coincided with  \n40 matrix mineralization and collagen organization, linking CL metabolism to both cellular  \n41 bioenergetics and extracellular matrix production. Our findings identify cardiolipin remodeling as  \n42 a metabolic checkpoint in osteogenesis and suggest that targeted modulation of CL pathways may  \n43 provide new therapeutic strategies for enhancing bone regeneration.  \n44  \n45  \n46 INTRODUCTION  \nbioRxiv preprint doi: [https://doi.org/10.64898/2025.12.22.696122](https://doi.org/10.64898/2025.12.22.696122); this version posted December 23, 2025. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made  \navailable under aCC-BY-ND 4.0 International license.  \n47 Osteogenic differentiation is a finely tuned biological process that results in the conversion  \n48 of mesenchymal stem cells (MSCs) into osteoblasts that produce bone through the deposition and  \n49 calcification of extracellular matrix (ECM) [1, 2] . T","cbCaikOmL80nz5TM","https://ap.wps.com/l/cbCaikOmL80nz5TM","pdf",3283731,25,"English","# Abstract\n# Introduction\n# Methods and Multimodal Profiling\n## LC–MS Lipidomics\n## Raman Spectroscopy\n## FLIM and Structural Imaging\n# Results: CL Remodeling and Osteogenic Differentiation\n## Lipid Signature and Enzyme Upregulation\n## Spatial Redistribution and Label-Free Mapping\n## Mitochondrial Bioenergetic Shift\n# Pathway Insights\n## Gene Ontology Enrichment\n## Protein–Protein Interaction Networks\n# Conclusion and Therapeutic Implications","[{\"question\":\"What question does this study address about cardiolipin in osteogenesis?\",\"answer\":\"The study investigates how cardiolipin (CL) remodeling contributes to osteogenic differentiation, which has been poorly defined despite CL’s role in mitochondrial bioenergetics.\"},{\"question\":\"Which multimodal techniques were used to study CL remodeling during differentiation?\",\"answer\":\"It combines untargeted LC–MS lipidomics, Raman spectroscopy, fluorescence lifetime imaging microscopy (FLIM), and structural imaging to examine lipid changes and their spatial and metabolic links to differentiation.\"},{\"question\":\"What metabolic shift was observed during osteogenic differentiation?\",\"answer\":\"FLIM data indicates a time-linked shift from glycolysis toward oxidative phosphorylation during differentiation, supported by structural and gene expression evidence.\"}]","Cardiolipin Remodeling as a Regulatory Switch in Osteogenesis - Insights from Multimodal Metabolic Imaging and Molecular Profiling | PDF",1790719277,63]