Differential expression of plasma extracellular vesicles microRNAs and exploration of their association with bone metabolism in childhood trauma participants treated in a psychosomatic clinic
IntroductionEarly life stress (ELS) impacts neurotransmitters and cell communication, potentially disrupting neurological and physiological processes. Recently, ELS has been implicated in impaired bone metabolism, with extracellular vesicles (EVs) and their cargo, microRNAs (miRNAs), might affecting...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-02-01
|
| Series: | Frontiers in Endocrinology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2025.1515910/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850229651124781056 |
|---|---|
| author | Yangyang He Yangyang He Karin Wuertz-Kozak Karin Wuertz-Kozak Petra Cazzanelli Sanne Houtenbos Sanne Houtenbos Francisco Garcia-Carrizo Francisco Garcia-Carrizo Tim J. Schulz Tim J. Schulz Tim J. Schulz Pia-Maria Wippert Pia-Maria Wippert |
| author_facet | Yangyang He Yangyang He Karin Wuertz-Kozak Karin Wuertz-Kozak Petra Cazzanelli Sanne Houtenbos Sanne Houtenbos Francisco Garcia-Carrizo Francisco Garcia-Carrizo Tim J. Schulz Tim J. Schulz Tim J. Schulz Pia-Maria Wippert Pia-Maria Wippert |
| author_sort | Yangyang He |
| collection | DOAJ |
| description | IntroductionEarly life stress (ELS) impacts neurotransmitters and cell communication, potentially disrupting neurological and physiological processes. Recently, ELS has been implicated in impaired bone metabolism, with extracellular vesicles (EVs) and their cargo, microRNAs (miRNAs), might affecting this process. This research aimed to elucidate the association between childhood trauma, a specific form of ELS, and bone metabolism through studying miRNA in EVs within three steps: firstly, examining alterations of EV miRNAs between ELS and controls, secondly analyzing associations between altered EV miRNAs and bone markers, and thirdly exploring the target gene prediction and enrichment pathways of altered EV miRNAs.MethodsThis study included a subgroup of the DEPREHA project (total n=208) from a psychosomatic clinic. Firstly, real-time quantitative PCR was performed on plasma EVs isolated from childhood trauma participants with depression (n=6) and matched healthy controls (n=9) to detect the differentially expressed EV miRNAs. Secondly, general linear regression models were employed to investigate the associations between specific EV miRNAs and circulating bone turnover markers (procollagen type 1 amino-terminal propeptide (P1NP), osteocalcin, and β-CrossLaps (CTx)), adjusting for depression as a potential confounder. Thirdly, the miRNA target gene networks and enriched pathways were explored based on altered EV miRNAs.ResultsThese analyses could be conducted on n=19 participants from the entire group (11 [57.9%] female; median [IQR] age, 35.00 [26.00] years), but finally n=15 participants were included for analyses. 22 out 380 EV miRNAs were differentially expressed between childhood trauma participants (6 up-regulated and 16 down-regulated) and healthy controls. Among these, miR-25-3p, miR-26b-5p, miR-451a, and miR-421 were associated with P1NP (bone formation marker) and CTx (bone resorption marker). MiR-26b-5p, miR-330-3p, and miR-542-5p were associated with osteocalcin (bone turnover marker). MiRNA target gene network prediction revealed highly associated target genes of dysregulated miRNAs, such as Trinucleotide Repeat Containing Adaptor 6B (TNRC6B), and enrichment analysis highlighted pathways including the forkhead box protein O (FoxO) signaling pathway.DiscussionsThis study explored the potential associations between childhood trauma and bone metabolism, due to the sample size and experimental group limitations, these associations should be validated in future experiments with larger sample sizes and different control group settings. |
| format | Article |
| id | doaj-art-632595ef02034058b03bb654e5efad2f |
| institution | OA Journals |
| issn | 1664-2392 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj-art-632595ef02034058b03bb654e5efad2f2025-08-20T02:04:09ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922025-02-011610.3389/fendo.2025.15159101515910Differential expression of plasma extracellular vesicles microRNAs and exploration of their association with bone metabolism in childhood trauma participants treated in a psychosomatic clinicYangyang He0Yangyang He1Karin Wuertz-Kozak2Karin Wuertz-Kozak3Petra Cazzanelli4Sanne Houtenbos5Sanne Houtenbos6Francisco Garcia-Carrizo7Francisco Garcia-Carrizo8Tim J. Schulz9Tim J. Schulz10Tim J. Schulz11Pia-Maria Wippert12Pia-Maria Wippert13Medical Sociology and Psychobiology, University of Potsdam, Potsdam, GermanyFaculty of Health Sciences Brandenburg, Joint Faculty of the University of Potsdam, The Brandenburg, Medical School Theodor Fontane and The Brandenburg University of Technology Cottbus—Senftenberg, Potsdam, GermanyDepartment of Biomedical Engineering, Rochester Institute of Technology, Rochester, NY, United StatesSchoen Clinic Munich Harlaching, Spine Center, Academic Teaching Hospital and Spine Research Institute of the Paracelsus Medical University Salzburg, Munich, GermanyDepartment of Biomedical Engineering, Rochester Institute of Technology, Rochester, NY, United StatesMedical Sociology and Psychobiology, University of Potsdam, Potsdam, GermanyFaculty of Health Sciences Brandenburg, Joint Faculty of the University of Potsdam, The Brandenburg, Medical School Theodor Fontane and The Brandenburg University of Technology Cottbus—Senftenberg, Potsdam, GermanyDepartment of Adipocyte Development and Nutrition, German Institute of Human Nutrition, Potsdam, GermanyGerman Center for Diabetes Research (DZD), München, GermanyDepartment of Adipocyte Development and Nutrition, German Institute of Human Nutrition, Potsdam, GermanyGerman Center for Diabetes Research (DZD), München, GermanyInstitute of Nutritional Science, University of Potsdam, Potsdam, GermanyMedical Sociology and Psychobiology, University of Potsdam, Potsdam, GermanyFaculty of Health Sciences Brandenburg, Joint Faculty of the University of Potsdam, The Brandenburg, Medical School Theodor Fontane and The Brandenburg University of Technology Cottbus—Senftenberg, Potsdam, GermanyIntroductionEarly life stress (ELS) impacts neurotransmitters and cell communication, potentially disrupting neurological and physiological processes. Recently, ELS has been implicated in impaired bone metabolism, with extracellular vesicles (EVs) and their cargo, microRNAs (miRNAs), might affecting this process. This research aimed to elucidate the association between childhood trauma, a specific form of ELS, and bone metabolism through studying miRNA in EVs within three steps: firstly, examining alterations of EV miRNAs between ELS and controls, secondly analyzing associations between altered EV miRNAs and bone markers, and thirdly exploring the target gene prediction and enrichment pathways of altered EV miRNAs.MethodsThis study included a subgroup of the DEPREHA project (total n=208) from a psychosomatic clinic. Firstly, real-time quantitative PCR was performed on plasma EVs isolated from childhood trauma participants with depression (n=6) and matched healthy controls (n=9) to detect the differentially expressed EV miRNAs. Secondly, general linear regression models were employed to investigate the associations between specific EV miRNAs and circulating bone turnover markers (procollagen type 1 amino-terminal propeptide (P1NP), osteocalcin, and β-CrossLaps (CTx)), adjusting for depression as a potential confounder. Thirdly, the miRNA target gene networks and enriched pathways were explored based on altered EV miRNAs.ResultsThese analyses could be conducted on n=19 participants from the entire group (11 [57.9%] female; median [IQR] age, 35.00 [26.00] years), but finally n=15 participants were included for analyses. 22 out 380 EV miRNAs were differentially expressed between childhood trauma participants (6 up-regulated and 16 down-regulated) and healthy controls. Among these, miR-25-3p, miR-26b-5p, miR-451a, and miR-421 were associated with P1NP (bone formation marker) and CTx (bone resorption marker). MiR-26b-5p, miR-330-3p, and miR-542-5p were associated with osteocalcin (bone turnover marker). MiRNA target gene network prediction revealed highly associated target genes of dysregulated miRNAs, such as Trinucleotide Repeat Containing Adaptor 6B (TNRC6B), and enrichment analysis highlighted pathways including the forkhead box protein O (FoxO) signaling pathway.DiscussionsThis study explored the potential associations between childhood trauma and bone metabolism, due to the sample size and experimental group limitations, these associations should be validated in future experiments with larger sample sizes and different control group settings.https://www.frontiersin.org/articles/10.3389/fendo.2025.1515910/fullmental disorderepigeneticsbone remodelingosteoporosisbone turnover markers |
| spellingShingle | Yangyang He Yangyang He Karin Wuertz-Kozak Karin Wuertz-Kozak Petra Cazzanelli Sanne Houtenbos Sanne Houtenbos Francisco Garcia-Carrizo Francisco Garcia-Carrizo Tim J. Schulz Tim J. Schulz Tim J. Schulz Pia-Maria Wippert Pia-Maria Wippert Differential expression of plasma extracellular vesicles microRNAs and exploration of their association with bone metabolism in childhood trauma participants treated in a psychosomatic clinic Frontiers in Endocrinology mental disorder epigenetics bone remodeling osteoporosis bone turnover markers |
| title | Differential expression of plasma extracellular vesicles microRNAs and exploration of their association with bone metabolism in childhood trauma participants treated in a psychosomatic clinic |
| title_full | Differential expression of plasma extracellular vesicles microRNAs and exploration of their association with bone metabolism in childhood trauma participants treated in a psychosomatic clinic |
| title_fullStr | Differential expression of plasma extracellular vesicles microRNAs and exploration of their association with bone metabolism in childhood trauma participants treated in a psychosomatic clinic |
| title_full_unstemmed | Differential expression of plasma extracellular vesicles microRNAs and exploration of their association with bone metabolism in childhood trauma participants treated in a psychosomatic clinic |
| title_short | Differential expression of plasma extracellular vesicles microRNAs and exploration of their association with bone metabolism in childhood trauma participants treated in a psychosomatic clinic |
| title_sort | differential expression of plasma extracellular vesicles micrornas and exploration of their association with bone metabolism in childhood trauma participants treated in a psychosomatic clinic |
| topic | mental disorder epigenetics bone remodeling osteoporosis bone turnover markers |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2025.1515910/full |
| work_keys_str_mv | AT yangyanghe differentialexpressionofplasmaextracellularvesiclesmicrornasandexplorationoftheirassociationwithbonemetabolisminchildhoodtraumaparticipantstreatedinapsychosomaticclinic AT yangyanghe differentialexpressionofplasmaextracellularvesiclesmicrornasandexplorationoftheirassociationwithbonemetabolisminchildhoodtraumaparticipantstreatedinapsychosomaticclinic AT karinwuertzkozak differentialexpressionofplasmaextracellularvesiclesmicrornasandexplorationoftheirassociationwithbonemetabolisminchildhoodtraumaparticipantstreatedinapsychosomaticclinic AT karinwuertzkozak differentialexpressionofplasmaextracellularvesiclesmicrornasandexplorationoftheirassociationwithbonemetabolisminchildhoodtraumaparticipantstreatedinapsychosomaticclinic AT petracazzanelli differentialexpressionofplasmaextracellularvesiclesmicrornasandexplorationoftheirassociationwithbonemetabolisminchildhoodtraumaparticipantstreatedinapsychosomaticclinic AT sannehoutenbos differentialexpressionofplasmaextracellularvesiclesmicrornasandexplorationoftheirassociationwithbonemetabolisminchildhoodtraumaparticipantstreatedinapsychosomaticclinic AT sannehoutenbos differentialexpressionofplasmaextracellularvesiclesmicrornasandexplorationoftheirassociationwithbonemetabolisminchildhoodtraumaparticipantstreatedinapsychosomaticclinic AT franciscogarciacarrizo differentialexpressionofplasmaextracellularvesiclesmicrornasandexplorationoftheirassociationwithbonemetabolisminchildhoodtraumaparticipantstreatedinapsychosomaticclinic AT franciscogarciacarrizo differentialexpressionofplasmaextracellularvesiclesmicrornasandexplorationoftheirassociationwithbonemetabolisminchildhoodtraumaparticipantstreatedinapsychosomaticclinic AT timjschulz differentialexpressionofplasmaextracellularvesiclesmicrornasandexplorationoftheirassociationwithbonemetabolisminchildhoodtraumaparticipantstreatedinapsychosomaticclinic AT timjschulz differentialexpressionofplasmaextracellularvesiclesmicrornasandexplorationoftheirassociationwithbonemetabolisminchildhoodtraumaparticipantstreatedinapsychosomaticclinic AT timjschulz differentialexpressionofplasmaextracellularvesiclesmicrornasandexplorationoftheirassociationwithbonemetabolisminchildhoodtraumaparticipantstreatedinapsychosomaticclinic AT piamariawippert differentialexpressionofplasmaextracellularvesiclesmicrornasandexplorationoftheirassociationwithbonemetabolisminchildhoodtraumaparticipantstreatedinapsychosomaticclinic AT piamariawippert differentialexpressionofplasmaextracellularvesiclesmicrornasandexplorationoftheirassociationwithbonemetabolisminchildhoodtraumaparticipantstreatedinapsychosomaticclinic |