Causal association analysis between blood metabolomes and osteopenia and therapeutic target prediction for mechanomedicine
Blood metabolomes have been linked to osteoporosis, yet the precise causal relationship with osteopenia, its preventable early stage, remains unclear. This study aimed to uncover the genetic causality between blood metabolomes and osteopenia, pinpointing potential targets for mechanomedicine. Utiliz...
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Elsevier
2025-09-01
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| Series: | Mechanobiology in Medicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2949907025000257 |
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| author | Ruobing Liu Yaru Huang Maogang Jiang Fei Xu Qilin Pei Jiajun Ma Youru Li Siqi Shen Bo Zhang Xiangyang Guo Jing Cai Wenwen Wang |
| author_facet | Ruobing Liu Yaru Huang Maogang Jiang Fei Xu Qilin Pei Jiajun Ma Youru Li Siqi Shen Bo Zhang Xiangyang Guo Jing Cai Wenwen Wang |
| author_sort | Ruobing Liu |
| collection | DOAJ |
| description | Blood metabolomes have been linked to osteoporosis, yet the precise causal relationship with osteopenia, its preventable early stage, remains unclear. This study aimed to uncover the genetic causality between blood metabolomes and osteopenia, pinpointing potential targets for mechanomedicine. Utilizing genome-wide association study summary statistics, we analyzed 1091 metabolites and 309 metabolite ratios from 8299 individuals, correlating them with total body bone mineral density (BMD) from 56,284 individuals in the IEU GWAS database and osteopenia data from 408,961 European populations. Through two-sample Mendelian randomization, we investigated the association between blood metabolomes and skeletal characteristics. We then conducted summary-data-based Mendelian randomization (MR) analysis and colocalization analyses to identify causal genes related to skeletal phenotypes, predicting therapeutic targets for osteopenia. Expression of potential targets in osteocytes under fluid shear stress (FSS) stimulation was tested using qRT-PCR to explore mechanical sensitivity and bone health mechanisms. Our findings revealed five metabolites affecting total body BMD and osteopenia, with biliverdin emerging as a potential protective factor against osteopenia (OR = 0.93, 95 %CI = 0.88–0.98, P = 0.009). Additionally, three genes—LRRC14, SLC22A16, and TNFRSF1A—were identified as potential therapeutic targets for osteopenia. Notably, LRRC14 and TNFRSF1A are also associated with other musculoskeletal diseases. In vitro experiments showed that FSS significantly increased LRRC14 expression in osteocytes, suggesting its potential as a mechanosensitive factor. This study identifies candidate blood metabolites and mechanomedicine targets for osteopenia, offering a scientific basis for new diagnostic and treatment strategies and deepening our understanding of bone mechanics response characteristics. |
| format | Article |
| id | doaj-art-95c98b59347448d2898aba46c80f2d9c |
| institution | Kabale University |
| issn | 2949-9070 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Mechanobiology in Medicine |
| spelling | doaj-art-95c98b59347448d2898aba46c80f2d9c2025-08-20T03:31:07ZengElsevierMechanobiology in Medicine2949-90702025-09-013310013710.1016/j.mbm.2025.100137Causal association analysis between blood metabolomes and osteopenia and therapeutic target prediction for mechanomedicineRuobing Liu0Yaru Huang1Maogang Jiang2Fei Xu3Qilin Pei4Jiajun Ma5Youru Li6Siqi Shen7Bo Zhang8Xiangyang Guo9Jing Cai10Wenwen Wang11Department of Biomedical Engineering, Fourth Military Medical University, Xi'an, 710032, ChinaDepartment of Health Statistics, School of Preventive Medicine, Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, Key Lab of Environmental Health Hazard Assessment and Protection of Shaanxi Province, Key Lab of Free Radical Biology and Medicine of Shaanxi Province, Fourth Military Medical University, Xi'an, 710032, Shaanxi Province, ChinaDepartment of Medical Engineering, The Second Affiliated Hospital of Air Force Medical University, Xi'an, 710038, ChinaDepartment of Radiation Oncology, Peking University Third Hospital, Beijing, 100191, ChinaDepartment of Biomedical Engineering, Fourth Military Medical University, Xi'an, 710032, ChinaDepartment of Aerospace Medicine, Fourth Military Medical University, Xi'an, 710032, ChinaDepartment of Biomedical Engineering, Fourth Military Medical University, Xi'an, 710032, ChinaDepartment of Biomedical Engineering, Fourth Military Medical University, Xi'an, 710032, ChinaDepartment of Biomedical Engineering, Fourth Military Medical University, Xi'an, 710032, ChinaDepartment of Biomedical Engineering, Fourth Military Medical University, Xi'an, 710032, ChinaDepartment of Biomedical Engineering, Fourth Military Medical University, Xi'an, 710032, China; College of Basic Medicine, Shaanxi University of Chinese Medicine, Xianyang, 712046, China; Corresponding author. College of Basic Medicine, Shaanxi University of Chinese Medicine, Xianyang, 712046, China.Department of Health Statistics, School of Preventive Medicine, Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, Key Lab of Environmental Health Hazard Assessment and Protection of Shaanxi Province, Key Lab of Free Radical Biology and Medicine of Shaanxi Province, Fourth Military Medical University, Xi'an, 710032, Shaanxi Province, China; Corresponding author. Department of Health Statistics, Fourth Military Medical University, #169 West Changle Road, Xi'an, China.Blood metabolomes have been linked to osteoporosis, yet the precise causal relationship with osteopenia, its preventable early stage, remains unclear. This study aimed to uncover the genetic causality between blood metabolomes and osteopenia, pinpointing potential targets for mechanomedicine. Utilizing genome-wide association study summary statistics, we analyzed 1091 metabolites and 309 metabolite ratios from 8299 individuals, correlating them with total body bone mineral density (BMD) from 56,284 individuals in the IEU GWAS database and osteopenia data from 408,961 European populations. Through two-sample Mendelian randomization, we investigated the association between blood metabolomes and skeletal characteristics. We then conducted summary-data-based Mendelian randomization (MR) analysis and colocalization analyses to identify causal genes related to skeletal phenotypes, predicting therapeutic targets for osteopenia. Expression of potential targets in osteocytes under fluid shear stress (FSS) stimulation was tested using qRT-PCR to explore mechanical sensitivity and bone health mechanisms. Our findings revealed five metabolites affecting total body BMD and osteopenia, with biliverdin emerging as a potential protective factor against osteopenia (OR = 0.93, 95 %CI = 0.88–0.98, P = 0.009). Additionally, three genes—LRRC14, SLC22A16, and TNFRSF1A—were identified as potential therapeutic targets for osteopenia. Notably, LRRC14 and TNFRSF1A are also associated with other musculoskeletal diseases. In vitro experiments showed that FSS significantly increased LRRC14 expression in osteocytes, suggesting its potential as a mechanosensitive factor. This study identifies candidate blood metabolites and mechanomedicine targets for osteopenia, offering a scientific basis for new diagnostic and treatment strategies and deepening our understanding of bone mechanics response characteristics.http://www.sciencedirect.com/science/article/pii/S2949907025000257Blood metabolomesOsteopeniaBone mineral densityMendelian randomizationGenome-wide association studyMechanomedicine |
| spellingShingle | Ruobing Liu Yaru Huang Maogang Jiang Fei Xu Qilin Pei Jiajun Ma Youru Li Siqi Shen Bo Zhang Xiangyang Guo Jing Cai Wenwen Wang Causal association analysis between blood metabolomes and osteopenia and therapeutic target prediction for mechanomedicine Mechanobiology in Medicine Blood metabolomes Osteopenia Bone mineral density Mendelian randomization Genome-wide association study Mechanomedicine |
| title | Causal association analysis between blood metabolomes and osteopenia and therapeutic target prediction for mechanomedicine |
| title_full | Causal association analysis between blood metabolomes and osteopenia and therapeutic target prediction for mechanomedicine |
| title_fullStr | Causal association analysis between blood metabolomes and osteopenia and therapeutic target prediction for mechanomedicine |
| title_full_unstemmed | Causal association analysis between blood metabolomes and osteopenia and therapeutic target prediction for mechanomedicine |
| title_short | Causal association analysis between blood metabolomes and osteopenia and therapeutic target prediction for mechanomedicine |
| title_sort | causal association analysis between blood metabolomes and osteopenia and therapeutic target prediction for mechanomedicine |
| topic | Blood metabolomes Osteopenia Bone mineral density Mendelian randomization Genome-wide association study Mechanomedicine |
| url | http://www.sciencedirect.com/science/article/pii/S2949907025000257 |
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