caa a22 4500 60552159X CHVBK 20210128100741.0 cr unu---uuuuu 210128e20150201xx s 000 0 eng 10.1007/s00223-014-9944-6 doi (NATIONALLICENCE)springer-10.1007/s00223-014-9944-6 Increased Endoplasmic Reticulum Stress in Mouse Osteocytes with Aging Alters Cox-2 Response to Mechanical Stimuli [Elektronische Daten] [Sreeda Chalil, Richard Jaspers, Ralph Manders, Jenneke Klein-Nulend, Astrid Bakker, Louise Deldicque] Aging reduces bone mass as well as the anabolic response of bone to mechanical stimuli, resulting in osteopenia. Endoplasmic reticulum (ER) stress impairs the response of myogenic cells to anabolic stimuli, and is involved in sarcopenia, but whether ER stress also contributes to osteopenia is unknown. Therefore, we tested whether ER stress exists in bones of aged mice, and whether this impairs the osteocyte response to mechanical stimulation. Primary osteocytes were obtained from long bones of adult (8months) and old (24-26months) mice, treated with or without the pharmacological ER stress inducer tunicamycin, and either or not subjected to mechanical loading by pulsating fluid flow (PFF). The osteocyte response to PFF was assessed by measuring cyclooxygenase-2 (Cox-2) mRNA levels and nitric oxide (NO) production. mRNA levels of ER stress markers were higher in old versus adult osteocytes (+40% for activating transcription factor-4, +120% for C/EBP homologous protein, and +120% for spliced X-box binding protein-1, p<0.05). The Cox-2 response to PFF was fourfold decreased in cells from old bones (p<0.001), while tunicamycin decreased PFF-induced Cox-2 expression by threefold in cells from adult bones (p<0.01). PFF increased NO production by 50% at 60min in osteocytes from old versus adult bones (p<0.01). In conclusion, our data indicate that the expression of several ER stress markers was higher in osteocytes from bones of old compared to adult mice. Since ER stress altered the response of osteocytes to mechanical loading, it could be a novel factor contributing to osteopenia. Springer Science+Business Media New York, 2014 ER stress nationallicence Unfolded protein response nationallicence Nitric oxide nationallicence Cyclooxygenase-2 nationallicence Osteopenia nationallicence Tunicamycin nationallicence Pulsating fluid flow nationallicence Chalil Sreeda Exercise Physiology Research Group, Department of Kinesiology, KU Leuven, Tervuursevest 101, Box 1500, 3001, Louvain, Belgium aut Jaspers Richard Laboratory for Myology, Move Research Institute Amsterdam, Faculty of Human Movement Sciences, VU University Amsterdam, Van der Boechorststraat 9, 1081, Amsterdam, The Netherlands aut Manders Ralph Department of Nutritional Sciences, Faculty of Health and Medical Sciences, University of Surrey, Duke of Kent Building, Guildford, GU2 7TE, Surrey, UK aut Klein-Nulend Jenneke Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), MOVE Research Institute Amsterdam, University of Amsterdam and VU University Amsterdam, Gustav Mahler Laan 3004, 1081, Amsterdam, The Netherlands aut Bakker Astrid Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), MOVE Research Institute Amsterdam, University of Amsterdam and VU University Amsterdam, Gustav Mahler Laan 3004, 1081, Amsterdam, The Netherlands aut Deldicque Louise Exercise Physiology Research Group, Department of Kinesiology, KU Leuven, Tervuursevest 101, Box 1500, 3001, Louvain, Belgium aut Calcified Tissue International Springer US; http://www.springer-ny.com 96/2(2015-02-01), 123-128 0171-967X 96:2<123 2015 96 223 https://doi.org/10.1007/s00223-014-9944-6 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00223-014-9944-6 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Chalil Sreeda Exercise Physiology Research Group, Department of Kinesiology, KU Leuven, Tervuursevest 101, Box 1500, 3001, Louvain, Belgium aut NATIONALLICENCE 700 1- Jaspers Richard Laboratory for Myology, Move Research Institute Amsterdam, Faculty of Human Movement Sciences, VU University Amsterdam, Van der Boechorststraat 9, 1081, Amsterdam, The Netherlands aut NATIONALLICENCE 700 1- Manders Ralph Department of Nutritional Sciences, Faculty of Health and Medical Sciences, University of Surrey, Duke of Kent Building, Guildford, GU2 7TE, Surrey, UK aut NATIONALLICENCE 700 1- Klein-Nulend Jenneke Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), MOVE Research Institute Amsterdam, University of Amsterdam and VU University Amsterdam, Gustav Mahler Laan 3004, 1081, Amsterdam, The Netherlands aut NATIONALLICENCE 700 1- Bakker Astrid Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), MOVE Research Institute Amsterdam, University of Amsterdam and VU University Amsterdam, Gustav Mahler Laan 3004, 1081, Amsterdam, The Netherlands aut NATIONALLICENCE 700 1- Deldicque Louise Exercise Physiology Research Group, Department of Kinesiology, KU Leuven, Tervuursevest 101, Box 1500, 3001, Louvain, Belgium aut NATIONALLICENCE 773 0- Calcified Tissue International Springer US; http://www.springer-ny.com 96/2(2015-02-01), 123-128 0171-967X 96:2<123 2015 96 223