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Effects of Early Life Stress on Bone Homeostasis in Mice and Humans


Wuertz-Kozak, Karin; Roszkowski, Martin; Cambria, Elena; Block, Andrea; Kuhn, Gisela A; Abele, Thea; Hitzl, Wolfgang; Drießlein, David; Müller, Ralph; Rapp, Michael A; Mansuy, Isabelle M; Peters, Eva M J; Wippert, Pia M (2020). Effects of Early Life Stress on Bone Homeostasis in Mice and Humans. International Journal of Molecular Sciences, 21(18):6634.

Abstract

Bone pathology is frequent in stressed individuals. A comprehensive examination of mechanisms linking life stress, depression and disturbed bone homeostasis is missing. In this translational study, mice exposed to early life stress (MSUS) were examined for bone microarchitecture (μCT), metabolism (qPCR/ELISA), and neuronal stress mediator expression (qPCR) and compared with a sample of depressive patients with or without early life stress by analyzing bone mineral density (BMD) (DXA) and metabolic changes in serum (osteocalcin, PINP, CTX-I). MSUS mice showed a significant decrease in NGF, NPYR1, VIPR1 and TACR1 expression, higher innervation density in bone, and increased serum levels of CTX-I, suggesting a milieu in favor of catabolic bone turnover. MSUS mice had a significantly lower body weight compared to control mice, and this caused minor effects on bone microarchitecture. Depressive patients with experiences of childhood neglect also showed a catabolic pattern. A significant reduction in BMD was observed in depressive patients with childhood abuse and stressful life events during childhood. Therefore, future studies on prevention and treatment strategies for both mental and bone disease should consider early life stress as a risk factor for bone pathologies.

Abstract

Bone pathology is frequent in stressed individuals. A comprehensive examination of mechanisms linking life stress, depression and disturbed bone homeostasis is missing. In this translational study, mice exposed to early life stress (MSUS) were examined for bone microarchitecture (μCT), metabolism (qPCR/ELISA), and neuronal stress mediator expression (qPCR) and compared with a sample of depressive patients with or without early life stress by analyzing bone mineral density (BMD) (DXA) and metabolic changes in serum (osteocalcin, PINP, CTX-I). MSUS mice showed a significant decrease in NGF, NPYR1, VIPR1 and TACR1 expression, higher innervation density in bone, and increased serum levels of CTX-I, suggesting a milieu in favor of catabolic bone turnover. MSUS mice had a significantly lower body weight compared to control mice, and this caused minor effects on bone microarchitecture. Depressive patients with experiences of childhood neglect also showed a catabolic pattern. A significant reduction in BMD was observed in depressive patients with childhood abuse and stressful life events during childhood. Therefore, future studies on prevention and treatment strategies for both mental and bone disease should consider early life stress as a risk factor for bone pathologies.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Brain Research Institute
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Scopus Subject Areas:Physical Sciences > Catalysis
Life Sciences > Molecular Biology
Physical Sciences > Spectroscopy
Physical Sciences > Computer Science Applications
Physical Sciences > Physical and Theoretical Chemistry
Physical Sciences > Organic Chemistry
Physical Sciences > Inorganic Chemistry
Uncontrolled Keywords:Physical and Theoretical Chemistry, Inorganic Chemistry, Organic Chemistry, Spectroscopy, Molecular Biology, Catalysis, General Medicine, Computer Science Applications
Language:English
Date:10 September 2020
Deposited On:18 Dec 2020 13:14
Last Modified:01 Jan 2021 21:08
Publisher:MDPI Publishing
ISSN:1422-0067
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.3390/ijms21186634
PubMed ID:32927845

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