title: Estrogen deficiency attenuates fluid flow-induced [Ca2+]ioscillations and mechanoresponsiveness of MLO-Y4 osteocytes.
abstract: It has been proposed that estrogen regulates the mechanosensitivity of osteocytes; however, the effects of estrogen deficiency that arises during postmenopausal osteoporosis on mechanical stimulation-induced calcium signaling in osteocytes remain elusive. Here, we pretreated MLO-Y4 osteocytes with 10 nM E2for 2, 3 and 5 d, then simulated postmenopausal conditions either by estrogen withdrawal (EW) from culture medium, or by inhibiting the estrogen receptor by using fulvestrant and estrogen (FE; ICI 182,780)in vitroWe investigated [Ca2+]ioscillations and mechanobiologic responses of osteocytes (EW and FE) that were exposed to oscillatory fluid flow (OFF; 1 Pa, 0.5 Hz). We demonstrated that estrogen treatment enhanced OFF-induced [Ca2+]ioscillations and that this effect was abrogated both by FE and EW. Moreover, osteocytes in both estrogen-depleted groups (EW and FE) had reduced levels of NO and prostaglandin E2release, down-regulated dentin matrix protein-1, sclerostin, osteopontin, osteocalcin, and alkaline phosphatase mRNA expression, and reduced F-actin fiber formation after OFF stimulation compared with estrogen-treated cells. We propose a link between estrogen deficiency and alterations in [Ca2+]i-mediated mechanosensitivity of osteocytes, which ultimately alter osteocyte function and differentiation.-Deepak, V., Kayastha, P., McNamara, L. M. Estrogen deficiency attenuates fluid flow-induced [Ca2+]ioscillations and mechanoresponsiveness of MLO-Y4 osteocytes.
authors.affiliation: Mechanobiology and Medical Device Research Group, Biomechanics Research Centre, Biomedical Engineering, College of Engineering and Informatics, National University of Ireland Galway, Galway, Ireland.
authors.forename: Vishwa
authors.initials: V
authors.lastname: Deepak
authors.affiliation: Mechanobiology and Medical Device Research Group, Biomechanics Research Centre, Biomedical Engineering, College of Engineering and Informatics, National University of Ireland Galway, Galway, Ireland.
authors.forename: Pushpalata
authors.initials: P
authors.lastname: Kayastha
authors.affiliation: Mechanobiology and Medical Device Research Group, Biomechanics Research Centre, Biomedical Engineering, College of Engineering and Informatics, National University of Ireland Galway, Galway, Ireland laoise.mcnamara@nuigalway.ie.
authors.forename: Laoise M
authors.initials: LM
authors.lastname: McNamara
mesh_terms: D000199:Actins / Q000502:physiology; D000818:Animals; D015415:Biomarkers; D001696:Biomechanical Phenomena; D020013:Calcium Signaling / Q000502:physiology*; D002460:Cell Line; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004967:Estrogens / Q000008:administration & dosage / Q000494:pharmacology*; D000077267:Fulvestrant; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D051379:Mice; D010011:Osteocytes / Q000187:drug effects / Q000378:metabolism*; D013314:Stress, Mechanical; D015854:Up-Regulation
chemical_list: D000199:Actins; D015415:Biomarkers; D004967:Estrogens; D000077267:Fulvestrant; D004958:Estradiol
keywords: E2; fluid shear stress; mechanobiology; menopause; osteoporosis