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Increased endoplasmic reticulum stress in mouse osteocytes with aging alters Cox-2 response to mechanical stimuli

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Chalil, Sreeda [KU Leuven] Jaspers, Richard T Manders, Ralph J Klein-Nulend, Jenneke Bakker, Astrid D Deldicque, Louise [UCL]

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.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès interdit
Publication date 2015
Language Anglais
Journal information "Calcified Tissue International" - Vol. 96, no. 2, p. 123-128 (2014)
Peer reviewed yes
Publisher Springer New York LLC (New York)
issn 0171-967X
e-issn 1432-0827
Publication status Publié
Affiliation UCL - SSS/IONS/CEMO-Pôle Cellulaire et moléculaire
Keywords ER stress ; Unfolded protein response ; Nitric oxide ; Cyclooxygenase-2 ; Osteopenia ; Tunicamycin ; Pulsating fluid flow
Links
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Bibliographic reference Chalil, Sreeda ; Jaspers, Richard T ; Manders, Ralph J ; Klein-Nulend, Jenneke ; Bakker, Astrid D ; et. al. Increased endoplasmic reticulum stress in mouse osteocytes with aging alters Cox-2 response to mechanical stimuli. In: Calcified Tissue International, Vol. 96, no. 2, p. 123-128 (2014)
Permanent URL http://hdl.handle.net/2078.1/160956