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 - TY - JOUR A1 - Franco-Obregon, Alfredo A1 - Cambria, Elena A1 - Greutert, Helen A1 - Wernas, Timon A1 - Hitzl, Wolfgang A1 - Egli, Marcel A1 - Sekiguchi, Miho A1 - Boos, Norbert A1 - Hausmann, Oliver A1 - Ferguson, Stephen J. A1 - Kobayashi, Hiroshi A1 - Würtz-Kozak, Karin T1 - TRPC6 in simulated microgravity of intervertebral disc cells JF - European Spine Journal N2 - Purpose Prolonged bed rest and microgravity in space cause intervertebral disc (IVD) degeneration. However, the underlying molecular mechanisms are not completely understood. Transient receptor potential canonical (TRPC) channels are implicated in mechanosensing of several tissues, but are poorly explored in IVDs. Methods Primary human IVD cells from surgical biopsies composed of both annulus fibrosus and nucleus pulposus (passage 1-2) were exposed to simulated microgravity and to the TRPC channel inhibitor SKF-96365 (SKF) for up to 5days. Proliferative capacity, cell cycle distribution, senescence and TRPC channel expression were analyzed. Results Both simulated microgravity and TRPC channel antagonism reduced the proliferative capacity of IVD cells and induced senescence. While significant changes in cell cycle distributions (reduction in G1 and accumulation in G2/M) were observed upon SKF treatment, the effect was small upon 3days of simulated microgravity. Finally, downregulation of TRPC6 was shown under simulated microgravity. Conclusions Simulated microgravity and TRPC channel inhibition both led to reduced proliferation and increased senescence. Furthermore, simulated microgravity reduced TRPC6 expression. IVD cell senescence and mechanotransduction may hence potentially be regulated by TRPC6 expression. This study thus reveals promising targets for future studies. KW - Intervertebral disc KW - Simulated microgravity KW - Senescence KW - TRP channels KW - Mechanotransduction KW - Gene expression Y1 - 2018 U6 - https://doi.org/10.1007/s00586-018-5688-8 SN - 0940-6719 SN - 1432-0932 VL - 27 IS - 10 SP - 2621 EP - 2630 PB - Springer CY - New York ER -