Phosphatidylcholine Ameliorates Palmitic Acid‐Induced Lipotoxicity by Facilitating Endoplasmic Reticulum and Mitochondria Contacts in Intervertebral Disc Degeneration
ABSTRACT Background Intervertebral disc degeneration (IDD) is a prevalent musculoskeletal disorder with substantial socioeconomic impacts. Despite its high prevalence, the pathogenesis of IDD remains unclear, and effective pharmacological interventions are lacking. This study aimed to investigate me...
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Wiley
2025-06-01
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| Online Access: | https://doi.org/10.1002/jsp2.70062 |
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| author | Shuangshuang Tu Yijun Dong Chuanfu Li Mingxin Jiang Liqun Duan Wenzhi Zhang Xi Chen |
| author_facet | Shuangshuang Tu Yijun Dong Chuanfu Li Mingxin Jiang Liqun Duan Wenzhi Zhang Xi Chen |
| author_sort | Shuangshuang Tu |
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| description | ABSTRACT Background Intervertebral disc degeneration (IDD) is a prevalent musculoskeletal disorder with substantial socioeconomic impacts. Despite its high prevalence, the pathogenesis of IDD remains unclear, and effective pharmacological interventions are lacking. This study aimed to investigate metabolic alterations in IDD and explore potential therapeutic targets by analyzing lipotoxicity‐related mechanisms in nucleus pulposus (NP) cells. Methods Metabolomics and magnetic resonance spectroscopy were utilized to profile metabolic changes in NP tissues from advanced‐stage IDD. Transcriptomics and metabolomics integration were performed to identify key regulatory pathways. In vitro experiments using human NP cells exposed to palmitic acid were conducted to evaluate endoplasmic reticulum (ER) stress, mitochondrial dysfunction, lipid droplet accumulation, and senescence. Phosphatidylcholine supplementation was tested for its ability to mitigate lipotoxicity, with ER‐mitochondria interactions and mitochondrial oxidation capacity assessed as mechanistic endpoints. Results Our findings revealed an abnormal lipotoxic condition in NP cells from advanced‐stage IDD. Furthermore, we identified abnormal accumulation of triglycerides and palmitic acid in NP cells from IDD. The palmitic acid accumulation resulted in endoplasmic reticulum stress, mitochondrial damage, lipid droplet accumulation, and senescence of NP cells. By integrating transcriptomics and metabolomics analyses, we discovered that phosphatidylcholine plays a role in regulating palmitic acid‐induced lipotoxicity. Notably, phosphatidylcholine level was found to be low in the endoplasmic reticulum and mitochondria of advanced‐stage NP cells. Phosphatidylcholine treatment alleviated palmitic acid‐induced lipid droplet accumulation and senescence of NP cells by modulating ER‐mitochondria contacts and mitochondrial oxidation capacity. Conclusion Phosphatidylcholine emerges as a potential therapeutic agent to counteract lipotoxic stress by modulating organelle interactions and mitochondrial function. These findings advance our understanding of IDD pathogenesis and provide a novel metabolic target for therapeutic development. |
| format | Article |
| id | doaj-art-dbee4e91a97745ef88daefaf7ea8232f |
| institution | Kabale University |
| issn | 2572-1143 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | JOR Spine |
| spelling | doaj-art-dbee4e91a97745ef88daefaf7ea8232f2025-08-20T03:27:11ZengWileyJOR Spine2572-11432025-06-0182n/an/a10.1002/jsp2.70062Phosphatidylcholine Ameliorates Palmitic Acid‐Induced Lipotoxicity by Facilitating Endoplasmic Reticulum and Mitochondria Contacts in Intervertebral Disc DegenerationShuangshuang Tu0Yijun Dong1Chuanfu Li2Mingxin Jiang3Liqun Duan4Wenzhi Zhang5Xi Chen6Department of Orthopedics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine University of Science and Technology of China Hefei ChinaDepartment of Orthopedics The First Affiliated Hospital of USTC, Provincial Hospital Affiliated to Anhui Medical University Hefei ChinaDepartment of Orthopedics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine University of Science and Technology of China Hefei ChinaDepartment of Orthopedics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine University of Science and Technology of China Hefei ChinaDepartment of Orthopedics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine University of Science and Technology of China Hefei ChinaDepartment of Orthopedics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine University of Science and Technology of China Hefei ChinaDepartment of Orthopedics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine University of Science and Technology of China Hefei ChinaABSTRACT Background Intervertebral disc degeneration (IDD) is a prevalent musculoskeletal disorder with substantial socioeconomic impacts. Despite its high prevalence, the pathogenesis of IDD remains unclear, and effective pharmacological interventions are lacking. This study aimed to investigate metabolic alterations in IDD and explore potential therapeutic targets by analyzing lipotoxicity‐related mechanisms in nucleus pulposus (NP) cells. Methods Metabolomics and magnetic resonance spectroscopy were utilized to profile metabolic changes in NP tissues from advanced‐stage IDD. Transcriptomics and metabolomics integration were performed to identify key regulatory pathways. In vitro experiments using human NP cells exposed to palmitic acid were conducted to evaluate endoplasmic reticulum (ER) stress, mitochondrial dysfunction, lipid droplet accumulation, and senescence. Phosphatidylcholine supplementation was tested for its ability to mitigate lipotoxicity, with ER‐mitochondria interactions and mitochondrial oxidation capacity assessed as mechanistic endpoints. Results Our findings revealed an abnormal lipotoxic condition in NP cells from advanced‐stage IDD. Furthermore, we identified abnormal accumulation of triglycerides and palmitic acid in NP cells from IDD. The palmitic acid accumulation resulted in endoplasmic reticulum stress, mitochondrial damage, lipid droplet accumulation, and senescence of NP cells. By integrating transcriptomics and metabolomics analyses, we discovered that phosphatidylcholine plays a role in regulating palmitic acid‐induced lipotoxicity. Notably, phosphatidylcholine level was found to be low in the endoplasmic reticulum and mitochondria of advanced‐stage NP cells. Phosphatidylcholine treatment alleviated palmitic acid‐induced lipid droplet accumulation and senescence of NP cells by modulating ER‐mitochondria contacts and mitochondrial oxidation capacity. Conclusion Phosphatidylcholine emerges as a potential therapeutic agent to counteract lipotoxic stress by modulating organelle interactions and mitochondrial function. These findings advance our understanding of IDD pathogenesis and provide a novel metabolic target for therapeutic development.https://doi.org/10.1002/jsp2.70062cell senescenceIDDlipotoxicitypalmitic acidphosphatidylcholine |
| spellingShingle | Shuangshuang Tu Yijun Dong Chuanfu Li Mingxin Jiang Liqun Duan Wenzhi Zhang Xi Chen Phosphatidylcholine Ameliorates Palmitic Acid‐Induced Lipotoxicity by Facilitating Endoplasmic Reticulum and Mitochondria Contacts in Intervertebral Disc Degeneration JOR Spine cell senescence IDD lipotoxicity palmitic acid phosphatidylcholine |
| title | Phosphatidylcholine Ameliorates Palmitic Acid‐Induced Lipotoxicity by Facilitating Endoplasmic Reticulum and Mitochondria Contacts in Intervertebral Disc Degeneration |
| title_full | Phosphatidylcholine Ameliorates Palmitic Acid‐Induced Lipotoxicity by Facilitating Endoplasmic Reticulum and Mitochondria Contacts in Intervertebral Disc Degeneration |
| title_fullStr | Phosphatidylcholine Ameliorates Palmitic Acid‐Induced Lipotoxicity by Facilitating Endoplasmic Reticulum and Mitochondria Contacts in Intervertebral Disc Degeneration |
| title_full_unstemmed | Phosphatidylcholine Ameliorates Palmitic Acid‐Induced Lipotoxicity by Facilitating Endoplasmic Reticulum and Mitochondria Contacts in Intervertebral Disc Degeneration |
| title_short | Phosphatidylcholine Ameliorates Palmitic Acid‐Induced Lipotoxicity by Facilitating Endoplasmic Reticulum and Mitochondria Contacts in Intervertebral Disc Degeneration |
| title_sort | phosphatidylcholine ameliorates palmitic acid induced lipotoxicity by facilitating endoplasmic reticulum and mitochondria contacts in intervertebral disc degeneration |
| topic | cell senescence IDD lipotoxicity palmitic acid phosphatidylcholine |
| url | https://doi.org/10.1002/jsp2.70062 |
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