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

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 2 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 [Ca 2+ ] 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 [Ca 2+ ] 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 E 2 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 2+ ] 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 [Ca 2+ ] i oscillations and mechanoresponsiveness of MLO‐Y4 osteocytes. FASEB J. 31, 3027–3039 (2017). www.fasebj.org