Discovery of Taurocholic Acid Sodium Hydrate as a Novel Repurposing Drug for Intervertebral Disc Degeneration by Targeting MAPK3
Objective Nowadays, more than 90% of people over 50 years suffer from intervertebral disc degeneration (IDD), but there are exist no ideal drugs. The aim of this study is to identify a new drug for IDD. Methods An approved small molecular drug library including 2040 small molecular compounds was use...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2024-01-01
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| Series: | Orthopaedic Surgery |
| Subjects: | |
| Online Access: | https://doi.org/10.1111/os.13909 |
| _version_ | 1797357529103073280 |
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| author | Ping Li Zesen Chen Keyu Meng Yanlin Chen Jiajia Xu Xin Xiang Xiuhua Wu Zhiping Huang Ruijun Lai Peng Li Zhongming Lai Xiang Ao Zhongyuan Liu Kaifan Yang Xiaochun Bai Zhongmin Zhang |
| author_facet | Ping Li Zesen Chen Keyu Meng Yanlin Chen Jiajia Xu Xin Xiang Xiuhua Wu Zhiping Huang Ruijun Lai Peng Li Zhongming Lai Xiang Ao Zhongyuan Liu Kaifan Yang Xiaochun Bai Zhongmin Zhang |
| author_sort | Ping Li |
| collection | DOAJ |
| description | Objective Nowadays, more than 90% of people over 50 years suffer from intervertebral disc degeneration (IDD), but there are exist no ideal drugs. The aim of this study is to identify a new drug for IDD. Methods An approved small molecular drug library including 2040 small molecular compounds was used here. We found that taurocholic acid sodium hydrate (NAT) could induce chondrogenesis and osteogenesis in mesenchymal stem cells (MSCs). Then, an in vivo mouse model of IDD was established and the coccygeal discs transcriptome analysis and surface plasmon resonance analysis (SPR) integrated with liquid chromatography–tandem mass spectrometry assay (LC‐MS) were performed in this study to study the therapy effect and target proteins of NAT for IDD. Micro‐CT was used to evaluate the cancellous bone. The expression of osteogenic (OCN, RNX2), chondrogenic (COL2A1, SOX9), and the target related (ERK1/2, p‐ERK1/2) proteins were detected. The alkaline phosphatase staining was performed to estimate osteogenic differentiation. Blood routine and blood biochemistry indexes were analyzed for the safety of NAT. Results The results showed that NAT could induce chondrogenesis and osteogenesis in MSCs. Further experiments confirmed NAT could ameliorate the secondary osteoporosis and delay the development of IDD in mice. Transcriptome analysis identified 128 common genes and eight Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways for NAT. SPR‐LC–MS assay detected 57 target proteins for NAT, including MAPK3 (mitogen‐activated protein kinase 3), also known as ERK1 (extracellular regulated protein kinase 1). Further verification experiment confirmed that NAT significantly reduced the expression of ERK1/2 phosphorylation. Conclusion NAT would induce chondrogenesis and osteogenesis of MSCs, ameliorate the secondary osteoporosis and delay the progression of IDD in mice by targeting MAPK3.Furthermore, MAPK3, especially the phosphorylation of MAPK3, would be a potential therapeutic target for IDD treatment. |
| first_indexed | 2024-03-08T14:46:28Z |
| format | Article |
| id | doaj.art-ea8132a1f55f46c29d3443927fc35031 |
| institution | Directory Open Access Journal |
| issn | 1757-7853 1757-7861 |
| language | English |
| last_indexed | 2024-03-08T14:46:28Z |
| publishDate | 2024-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Orthopaedic Surgery |
| spelling | doaj.art-ea8132a1f55f46c29d3443927fc350312024-01-11T09:51:57ZengWileyOrthopaedic Surgery1757-78531757-78612024-01-0116118319510.1111/os.13909Discovery of Taurocholic Acid Sodium Hydrate as a Novel Repurposing Drug for Intervertebral Disc Degeneration by Targeting MAPK3Ping Li0Zesen Chen1Keyu Meng2Yanlin Chen3Jiajia Xu4Xin Xiang5Xiuhua Wu6Zhiping Huang7Ruijun Lai8Peng Li9Zhongming Lai10Xiang Ao11Zhongyuan Liu12Kaifan Yang13Xiaochun Bai14Zhongmin Zhang15Division of Spine Surgery, Department of Orthopaedics, Nanfang Hospital Southern Medical University Guangzhou ChinaDivision of Spine Surgery, Department of Orthopaedics, Nanfang Hospital Southern Medical University Guangzhou ChinaDivision of Spine Surgery, Department of Orthopaedics, Nanfang Hospital Southern Medical University Guangzhou ChinaDivision of Spine Surgery, Department of Orthopaedics, Nanfang Hospital Southern Medical University Guangzhou ChinaDivision of Spine Surgery, Department of Orthopaedics, Nanfang Hospital Southern Medical University Guangzhou ChinaDivision of Spine Surgery, Department of Orthopaedics, Nanfang Hospital Southern Medical University Guangzhou ChinaDivision of Spine Surgery, Department of Orthopaedics, Nanfang Hospital Southern Medical University Guangzhou ChinaDivision of Spine Surgery, Department of Orthopaedics, Nanfang Hospital Southern Medical University Guangzhou ChinaGuangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Department of Cell Biology, School of Basic Medical Sciences Southern Medical University Guangzhou ChinaDivision of Spine Surgery, Department of Orthopaedics, Nanfang Hospital Southern Medical University Guangzhou ChinaDivision of Spine Surgery, Department of Orthopaedics, Nanfang Hospital Southern Medical University Guangzhou ChinaDivision of Spine Surgery, Department of Orthopaedics, Nanfang Hospital Southern Medical University Guangzhou ChinaDivision of Spine Surgery, Department of Orthopaedics, Nanfang Hospital Southern Medical University Guangzhou ChinaDivision of Spine Surgery, Department of Orthopaedics, Nanfang Hospital Southern Medical University Guangzhou ChinaGuangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Department of Cell Biology, School of Basic Medical Sciences Southern Medical University Guangzhou ChinaDivision of Spine Surgery, Department of Orthopaedics, Nanfang Hospital Southern Medical University Guangzhou ChinaObjective Nowadays, more than 90% of people over 50 years suffer from intervertebral disc degeneration (IDD), but there are exist no ideal drugs. The aim of this study is to identify a new drug for IDD. Methods An approved small molecular drug library including 2040 small molecular compounds was used here. We found that taurocholic acid sodium hydrate (NAT) could induce chondrogenesis and osteogenesis in mesenchymal stem cells (MSCs). Then, an in vivo mouse model of IDD was established and the coccygeal discs transcriptome analysis and surface plasmon resonance analysis (SPR) integrated with liquid chromatography–tandem mass spectrometry assay (LC‐MS) were performed in this study to study the therapy effect and target proteins of NAT for IDD. Micro‐CT was used to evaluate the cancellous bone. The expression of osteogenic (OCN, RNX2), chondrogenic (COL2A1, SOX9), and the target related (ERK1/2, p‐ERK1/2) proteins were detected. The alkaline phosphatase staining was performed to estimate osteogenic differentiation. Blood routine and blood biochemistry indexes were analyzed for the safety of NAT. Results The results showed that NAT could induce chondrogenesis and osteogenesis in MSCs. Further experiments confirmed NAT could ameliorate the secondary osteoporosis and delay the development of IDD in mice. Transcriptome analysis identified 128 common genes and eight Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways for NAT. SPR‐LC–MS assay detected 57 target proteins for NAT, including MAPK3 (mitogen‐activated protein kinase 3), also known as ERK1 (extracellular regulated protein kinase 1). Further verification experiment confirmed that NAT significantly reduced the expression of ERK1/2 phosphorylation. Conclusion NAT would induce chondrogenesis and osteogenesis of MSCs, ameliorate the secondary osteoporosis and delay the progression of IDD in mice by targeting MAPK3.Furthermore, MAPK3, especially the phosphorylation of MAPK3, would be a potential therapeutic target for IDD treatment.https://doi.org/10.1111/os.13909ChondrogenesisIntervertebral Disc Degeneration (IDD)Mesenchymal Stem Cells (MSCs)OsteogenesisTaurocholic Acid Sodium Salt Hydrate (NAT) |
| spellingShingle | Ping Li Zesen Chen Keyu Meng Yanlin Chen Jiajia Xu Xin Xiang Xiuhua Wu Zhiping Huang Ruijun Lai Peng Li Zhongming Lai Xiang Ao Zhongyuan Liu Kaifan Yang Xiaochun Bai Zhongmin Zhang Discovery of Taurocholic Acid Sodium Hydrate as a Novel Repurposing Drug for Intervertebral Disc Degeneration by Targeting MAPK3 Orthopaedic Surgery Chondrogenesis Intervertebral Disc Degeneration (IDD) Mesenchymal Stem Cells (MSCs) Osteogenesis Taurocholic Acid Sodium Salt Hydrate (NAT) |
| title | Discovery of Taurocholic Acid Sodium Hydrate as a Novel Repurposing Drug for Intervertebral Disc Degeneration by Targeting MAPK3 |
| title_full | Discovery of Taurocholic Acid Sodium Hydrate as a Novel Repurposing Drug for Intervertebral Disc Degeneration by Targeting MAPK3 |
| title_fullStr | Discovery of Taurocholic Acid Sodium Hydrate as a Novel Repurposing Drug for Intervertebral Disc Degeneration by Targeting MAPK3 |
| title_full_unstemmed | Discovery of Taurocholic Acid Sodium Hydrate as a Novel Repurposing Drug for Intervertebral Disc Degeneration by Targeting MAPK3 |
| title_short | Discovery of Taurocholic Acid Sodium Hydrate as a Novel Repurposing Drug for Intervertebral Disc Degeneration by Targeting MAPK3 |
| title_sort | discovery of taurocholic acid sodium hydrate as a novel repurposing drug for intervertebral disc degeneration by targeting mapk3 |
| topic | Chondrogenesis Intervertebral Disc Degeneration (IDD) Mesenchymal Stem Cells (MSCs) Osteogenesis Taurocholic Acid Sodium Salt Hydrate (NAT) |
| url | https://doi.org/10.1111/os.13909 |
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