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estrogen deficiency attenuates fluid flow–induced [ca 2+ ] i oscillations and mechanoresponsiveness of mlo-y4 osteocytes

Deepak, Vishwa
; 
Kayastha, Pushpalata
; 
McNamara, Laoise M.
Repository DOI
Publication Date
2017-03-31
Keywords
e-2, mechanobiology, fluid shear stress, osteoporosis, menopause, dentin matrix protein-1, serum sclerostin levels, stress in-vitro, bone-cells, nitric-oxide, mechanical strain, receptor-alpha, postmenopausal women, gene-expression, osteoblasts
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Article
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Deepak, Vishwa; Kayastha, Pushpalata; McNamara, Laoise M. (2017). estrogen deficiency attenuates fluid flow–induced [ca 2+ ] i oscillations and mechanoresponsiveness of mlo-y4 osteocytes . The FASEB Journal 31 (7), 3027-3039
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 E2 for 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 vitro. We investigated [Ca2+](i) oscillations 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+](i) oscillations 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 E2 release, 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+](i) oscillations and mechanoresponsiveness of MLO-Y4 osteocytes.
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Publisher
FASEB
Publisher DOI
10.1096/fj.201601280r
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Attribution-NonCommercial-NoDerivs 3.0 Ireland
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Externally hosted open access publications with University of Galway authors (2)