TY - GEN A1 - Wippert, Pia-Maria A1 - Rector, Michael V. A1 - Kuhn, Gisela A1 - Wuertz-Kozak, Karin T1 - Stress and Alterations in Bones BT - An Interdisciplinary Perspective N2 - Decades of research have demonstrated that physical stress (PS) stimulates bone remodeling and affects bone structure and function through complex mechanotransduction mechanisms. Recent research has laid ground to the hypothesis that mental stress (MS) also influences bone biology, eventually leading to osteoporosis and increased bone fracture risk. These effects are likely exerted by modulation of hypothalamic–pituitary–adrenal axis activity, resulting in an altered release of growth hormones, glucocorticoids and cytokines, as demonstrated in human and animal studies. Furthermore, molecular cross talk between mental and PS is thought to exist, with either synergistic or preventative effects on bone disease progression depending on the characteristics of the applied stressor. This mini review will explain the emerging concept of MS as an important player in bone adaptation and its potential cross talk with PS by summarizing the current state of knowledge, highlighting newly evolving notions (such as intergenerational transmission of stress and its epigenetic modifications affecting bone) and proposing new research directions. T3 - Zweitveröffentlichungen der Universität Potsdam : Humanwissenschaftliche Reihe - 323 KW - biomechanics KW - bone–brain–nervous system interactions KW - endocrine pathways KW - exercise KW - osteoporosis Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-395866 ER - TY - JOUR A1 - Wippert, Pia-Maria A1 - Rector, Michael V. A1 - Kuhn, Gisela A1 - Wuertz-Kozak, Karin T1 - Stress and Alterations in Bones BT - An Interdisciplinary Perspective JF - Frontiers in endocrinology N2 - Decades of research have demonstrated that physical stress (PS) stimulates bone remodeling and affects bone structure and function through complex mechanotransduction mechanisms. Recent research has laid ground to the hypothesis that mental stress (MS) also influences bone biology, eventually leading to osteoporosis and increased bone fracture risk. These effects are likely exerted by modulation of hypothalamic–pituitary–adrenal axis activity, resulting in an altered release of growth hormones, glucocorticoids and cytokines, as demonstrated in human and animal studies. Furthermore, molecular cross talk between mental and PS is thought to exist, with either synergistic or preventative effects on bone disease progression depending on the characteristics of the applied stressor. This mini review will explain the emerging concept of MS as an important player in bone adaptation and its potential cross talk with PS by summarizing the current state of knowledge, highlighting newly evolving notions (such as intergenerational transmission of stress and its epigenetic modifications affecting bone) and proposing new research directions. KW - biomechanics KW - bone–brain–nervous system interactions KW - endocrine pathways KW - osteoporosis KW - exercise Y1 - 2017 U6 - https://doi.org/10.3389/fendo.2017.00096 SN - 1664-2392 VL - 8 PB - Frontiers Research Foundation CY - Lausanne ER - TY - JOUR A1 - Krupkova, Olga A1 - Sadowska, Aleksandra A1 - Kameda, Takuya A1 - Hitzl, Wolfgang A1 - Hausmann, Oliver Nic A1 - Klasen, Jürgen A1 - Wuertz-Kozak, Karin T1 - p38 MaPK Facilitates crosstalk Between endoplasmic reticulum stress and IL-6 release in the intervertebral Disc JF - Frontiers in Immunology N2 - Degenerative disc disease is associated with increased expression of pro-inflammatory cytokines in the intervertebral disc (IVD). However, it is not completely clear how inflammation arises in the IVD and which cellular compartments are involved in this process. Recently, the endoplasmic reticulum (ER) has emerged as a possible modulator of inflammation in age-related disorders. In addition, ER stress has been associated with the microenvironment of degenerated IVDs. Therefore, the aim of this study was to analyze the effects of ER stress on inflammatory responses in degenerated human IVDs and associated molecular mechanisms. Gene expression of ER stress marker GRP78 and pro-inflammatory cytokines IL-6, IL-8, IL-1 beta, and TNF-alpha was analyzed in human surgical IVD samples (n = 51, Pfirrmann grade 2-5). The expression of GRP78 positively correlated with the degeneration grade in lumbar IVDs and IL-6, but not with IL-1 beta and TNF-alpha. Another set of human surgical IVD samples (n = 25) was used to prepare primary cell cultures. ER stress inducer thapsigargin (Tg, 100 and 500 nM) activated gene and protein expression of IL-6 and induced phosphorylation of p38 MAPK. Both inhibition of p38 MAPK by SB203580 (10 mu M) and knockdown of ER stress effector CCAAT-enhancer-binding protein homologous protein (CHOP) reduced gene and protein expression of IL-6 in Tg-treated cells. Furthermore, the effects of an inflammatory microenvironment on ER stress were tested. TNF-alpha (5 and 10 ng/mL) did not activate ER stress, while IL-1 beta (5 and 10 ng/mL) activated gene and protein expression of GRP78, but did not influence [Ca2+](i) flux and expression of CHOP, indicating that pro-inflammatory cytokines alone may not induce ER stress in vivo. This study showed that IL-6 release in the IVD can be initiated following ER stress and that ER stress mediates IL-6 release through p38 MAPK and CHOP. Therapeutic targeting of ER stress response may reduce the consequences of the harsh microenvironment in degenerated IVD. KW - intervertebral disc KW - inflammation KW - endoplasmic reticulum stress KW - p38 MAPK KW - CHOP KW - GADD153 KW - GRP78 KW - IL-6 Y1 - 2018 U6 - https://doi.org/10.3389/fimmu.2018.01706 SN - 1664-3224 VL - 9 PB - Frontiers Research Foundation CY - Lausanne ER - TY - GEN A1 - Wuertz-Kozak, Karin A1 - Roszkowski, Martin A1 - Cambria, Elena A1 - Block, Andrea A1 - Kuhn, Gisela A. A1 - Abele, Thea A1 - Hitzl, Wolfgang A1 - Drießlein, David A1 - Müller, Ralph A1 - Rapp, Michael Armin A1 - Mansuy, Isabelle M. A1 - Peters, Eva M. J. A1 - Wippert, Pia-Maria T1 - Effects of Early Life Stress on Bone Homeostasis in Mice and Humans T2 - Postprints der Universität Potsdam : Humanwissenschaftliche Reihe N2 - 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. T3 - Zweitveröffentlichungen der Universität Potsdam : Humanwissenschaftliche Reihe - 670 KW - psychosocial stress KW - bone pathologies KW - osteoporosis KW - bone mineral density KW - childhood KW - neuroendocrine Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-485324 SN - 1866-8364 IS - 670 ER - TY - JOUR A1 - Wuertz-Kozak, Karin A1 - Roszkowski, Martin A1 - Cambria, Elena A1 - Block, Andrea A1 - Kuhn, Gisela A. A1 - Abele, Thea A1 - Hitzl, Wolfgang A1 - Drießlein, David A1 - Müller, Ralph A1 - Rapp, Michael Armin A1 - Mansuy, Isabelle M. A1 - Peters, Eva M. J. A1 - Wippert, Pia-Maria T1 - Effects of Early Life Stress on Bone Homeostasis in Mice and Humans JF - International Journal of Molecular Sciences N2 - 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. KW - psychosocial stress KW - bone pathologies KW - osteoporosis KW - bone mineral density KW - childhood KW - neuroendocrine Y1 - 2020 U6 - https://doi.org/10.3390/ijms21186634 SN - 1422-0067 VL - 21 IS - 18 PB - Molecular Diversity Preservation International CY - Basel ER -