Abstract
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 (8 months) and old (24–26 months) 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 60 min 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.
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Acknowledgments
This research was funded by the European Commission through MOVE-AGE, an Erasmus Mundus Joint Doctorate program (2012–2016). The authors would like to thank Cornelis Semeins, Guus Baan, and Gerard de Wit for technical assistance.
Conflict of interest
Sreeda Chalil, Richard T Jaspers, Ralph J Manders, Jenneke Klein-Nulend, Astrid D Bakker, and Louise Deldicque declare no conflict of interest.
Human and Animal Rights and Informed Consent
The use of animals in this study was approved by the animal care and use committee of the VU University Amsterdam.
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Chalil, S., Jaspers, R.T., Manders, R.J. et al. Increased Endoplasmic Reticulum Stress in Mouse Osteocytes with Aging Alters Cox-2 Response to Mechanical Stimuli. Calcif Tissue Int 96, 123–128 (2015). https://doi.org/10.1007/s00223-014-9944-6
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DOI: https://doi.org/10.1007/s00223-014-9944-6