Estrogen deficiency attenuates fluid flow-induced [Ca 2+ ] i oscillations and mechanoresponsiveness of MLO-Y4 osteocytes

• Published in: The FASEB journal Vol. 31; no. 7; p. 3027
• Main Authors: Deepak, Vishwa, Kayastha, Pushpalata, McNamara, Laoise M
• Format: Journal Article
• Language: English
• Published: United States 01.07.2017
• Subjects: Actins - physiology; Animals; Biomarkers; Biomechanical Phenomena; Calcium Signaling - physiology; Cell Line; Estradiol - analogs & derivatives; Estradiol - pharmacology; Estrogens - administration & dosage; Estrogens - pharmacology; Gene Expression Regulation - drug effects; Gene Expression Regulation - physiology; Mice; Osteocytes - drug effects; Osteocytes - metabolism; Stress, Mechanical; Up-Regulation; mechanobiology; menopause; osteoporosis; E2; fluid shear stress
• ISSN: 1530-6860
• DOI: 10.1096/fj.201601280R

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 E 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) We investigated [Ca ] 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 [Ca ] 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 E 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 [Ca ] -mediated mechanosensitivity of osteocytes, which ultimately alter osteocyte function and differentiation.-Deepak, V., Kayastha, P., McNamara, L. M. Estrogen deficiency attenuates fluid flow-induced [Ca ] oscillations and mechanoresponsiveness of MLO-Y4 osteocytes.