Immune Cells as Mediators of Lipidome Influence on Osteoporosis: Evidence from a Mediation Analysis
<b>Background</b>: Although clinical studies have indicated a possible association between dyslipidemia and osteoporosis, the underlying genetic basis and mechanistic pathways remain insufficiently defined. Most prior research has concentrated on conventional lipid markers, which are pro...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-05-01
|
| Series: | Diagnostics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2075-4418/15/10/1287 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850257045658271744 |
|---|---|
| author | Jiheng Xiao Wei Zhou Jiatai He Yanbin Zhu Yingze Zhang Liming Xiong |
| author_facet | Jiheng Xiao Wei Zhou Jiatai He Yanbin Zhu Yingze Zhang Liming Xiong |
| author_sort | Jiheng Xiao |
| collection | DOAJ |
| description | <b>Background</b>: Although clinical studies have indicated a possible association between dyslipidemia and osteoporosis, the underlying genetic basis and mechanistic pathways remain insufficiently defined. Most prior research has concentrated on conventional lipid markers, which are prone to confounding and limit causal inference. Exploring lipidomic profiles offers a more comprehensive view of lipid metabolism and may reveal novel genetic links beyond traditional lipid traits. Additionally, alterations in immune cell function, often triggered by metabolic disturbances, may contribute to osteoporosis development; however, the potential mediating role of immune cells in the lipid–bone axis has not been systematically investigated. <b>Methods</b>: A total of 179 lipid species across 13 lipid classes were analyzed in 7174 Finnish individuals from the GeneRISK cohort. Genome-Wide Association Study (GWAS) summary statistics for osteoporosis and 731 immune cell immunophenotypes were sourced from the GWAS Catalog. A two-step, two-sample Mendelian randomization analysis, using inverse variance weighting (IVW), was conducted to explore the potential causal effects of lipids on osteoporosis and the mediating role of immune cells in the relationship between lipids and osteoporosis. <b>Results</b>: Mendelian randomization analysis indicated that triacylglycerol levels of 48:0 were possibly associated with an increased risk of osteoporosis (IVW: odds ratio [OR] 1.1320, 95% CI 1.0401–1.2321; <i>p</i> = 0.004), while triacylglycerol levels of 48:3 appeared to be associated with a reduced risk of osteoporosis (IVW: OR 0.9053, 95% CI 0.8364–0.9800; <i>p</i> = 0.014). Two statistically significant mediating effects were identified: First, IgD− CD38dim %B cells appeared to partially negatively mediate the association between triacylglycerol levels of 48:3 and osteoporosis, with a negative mediating effect of −0.00669 (95% CI: −0.0214, 0.00805), which accounted for 6.73% of the total effect. That is, the protective effect of triacylglycerol levels of 48:3 against osteoporosis was attenuated by IgD− CD38dim %B cells. Second, HLA DR++ monocytes% leukocytes also partially negatively mediated this relationship, with a mediating effect of −0.023 (95% CI: −0.0434, −0.00266), accounting for 23.2% of the total effect. This indicates that other immune cells, HLA DR++ monocytes %leukocytes, resisted the protective effect of triacylglycerol levels of 48:3 against osteoporosis, with a weakening effect stronger than that of IgD− CD38dim %B cells. <b>Conclusions</b>: Our findings contribute to the growing understanding of the potential causal relationships and shared pathogenic mechanisms between dyslipidemia and osteoporosis. The results suggest that the potential genetic effects of plasma lipid metabolites on osteoporosis may be partially down-regulated by specific kinds of immune cells. |
| format | Article |
| id | doaj-art-d5cbde71c1434bb7be03c359fc84d952 |
| institution | OA Journals |
| issn | 2075-4418 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Diagnostics |
| spelling | doaj-art-d5cbde71c1434bb7be03c359fc84d9522025-08-20T01:56:31ZengMDPI AGDiagnostics2075-44182025-05-011510128710.3390/diagnostics15101287Immune Cells as Mediators of Lipidome Influence on Osteoporosis: Evidence from a Mediation AnalysisJiheng Xiao0Wei Zhou1Jiatai He2Yanbin Zhu3Yingze Zhang4Liming Xiong5Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, ChinaDepartment of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, ChinaDepartment of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, ChinaDepartment of Orthopaedic Surgery, Third Hospital of Hebei Medical University, Shijiazhuang 050051, ChinaDepartment of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, ChinaDepartment of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China<b>Background</b>: Although clinical studies have indicated a possible association between dyslipidemia and osteoporosis, the underlying genetic basis and mechanistic pathways remain insufficiently defined. Most prior research has concentrated on conventional lipid markers, which are prone to confounding and limit causal inference. Exploring lipidomic profiles offers a more comprehensive view of lipid metabolism and may reveal novel genetic links beyond traditional lipid traits. Additionally, alterations in immune cell function, often triggered by metabolic disturbances, may contribute to osteoporosis development; however, the potential mediating role of immune cells in the lipid–bone axis has not been systematically investigated. <b>Methods</b>: A total of 179 lipid species across 13 lipid classes were analyzed in 7174 Finnish individuals from the GeneRISK cohort. Genome-Wide Association Study (GWAS) summary statistics for osteoporosis and 731 immune cell immunophenotypes were sourced from the GWAS Catalog. A two-step, two-sample Mendelian randomization analysis, using inverse variance weighting (IVW), was conducted to explore the potential causal effects of lipids on osteoporosis and the mediating role of immune cells in the relationship between lipids and osteoporosis. <b>Results</b>: Mendelian randomization analysis indicated that triacylglycerol levels of 48:0 were possibly associated with an increased risk of osteoporosis (IVW: odds ratio [OR] 1.1320, 95% CI 1.0401–1.2321; <i>p</i> = 0.004), while triacylglycerol levels of 48:3 appeared to be associated with a reduced risk of osteoporosis (IVW: OR 0.9053, 95% CI 0.8364–0.9800; <i>p</i> = 0.014). Two statistically significant mediating effects were identified: First, IgD− CD38dim %B cells appeared to partially negatively mediate the association between triacylglycerol levels of 48:3 and osteoporosis, with a negative mediating effect of −0.00669 (95% CI: −0.0214, 0.00805), which accounted for 6.73% of the total effect. That is, the protective effect of triacylglycerol levels of 48:3 against osteoporosis was attenuated by IgD− CD38dim %B cells. Second, HLA DR++ monocytes% leukocytes also partially negatively mediated this relationship, with a mediating effect of −0.023 (95% CI: −0.0434, −0.00266), accounting for 23.2% of the total effect. This indicates that other immune cells, HLA DR++ monocytes %leukocytes, resisted the protective effect of triacylglycerol levels of 48:3 against osteoporosis, with a weakening effect stronger than that of IgD− CD38dim %B cells. <b>Conclusions</b>: Our findings contribute to the growing understanding of the potential causal relationships and shared pathogenic mechanisms between dyslipidemia and osteoporosis. The results suggest that the potential genetic effects of plasma lipid metabolites on osteoporosis may be partially down-regulated by specific kinds of immune cells.https://www.mdpi.com/2075-4418/15/10/1287lipidomeimmune cellsosteoporosismendelian randomizationmediating effect |
| spellingShingle | Jiheng Xiao Wei Zhou Jiatai He Yanbin Zhu Yingze Zhang Liming Xiong Immune Cells as Mediators of Lipidome Influence on Osteoporosis: Evidence from a Mediation Analysis Diagnostics lipidome immune cells osteoporosis mendelian randomization mediating effect |
| title | Immune Cells as Mediators of Lipidome Influence on Osteoporosis: Evidence from a Mediation Analysis |
| title_full | Immune Cells as Mediators of Lipidome Influence on Osteoporosis: Evidence from a Mediation Analysis |
| title_fullStr | Immune Cells as Mediators of Lipidome Influence on Osteoporosis: Evidence from a Mediation Analysis |
| title_full_unstemmed | Immune Cells as Mediators of Lipidome Influence on Osteoporosis: Evidence from a Mediation Analysis |
| title_short | Immune Cells as Mediators of Lipidome Influence on Osteoporosis: Evidence from a Mediation Analysis |
| title_sort | immune cells as mediators of lipidome influence on osteoporosis evidence from a mediation analysis |
| topic | lipidome immune cells osteoporosis mendelian randomization mediating effect |
| url | https://www.mdpi.com/2075-4418/15/10/1287 |
| work_keys_str_mv | AT jihengxiao immunecellsasmediatorsoflipidomeinfluenceonosteoporosisevidencefromamediationanalysis AT weizhou immunecellsasmediatorsoflipidomeinfluenceonosteoporosisevidencefromamediationanalysis AT jiataihe immunecellsasmediatorsoflipidomeinfluenceonosteoporosisevidencefromamediationanalysis AT yanbinzhu immunecellsasmediatorsoflipidomeinfluenceonosteoporosisevidencefromamediationanalysis AT yingzezhang immunecellsasmediatorsoflipidomeinfluenceonosteoporosisevidencefromamediationanalysis AT limingxiong immunecellsasmediatorsoflipidomeinfluenceonosteoporosisevidencefromamediationanalysis |