Estrogen withdrawal alters cytoskeletal and primary ciliary dynamics resulting in increased Hedgehog and osteoclastogenic paracrine signalling in osteocytes

Abstract Estrogen deficiency during post-menopausal osteoporosis leads to osteoclastogenesis and bone loss. Increased pro-osteoclastogenic signalling (RANKL/OPG) by osteocytes occurs following estrogen withdrawal (EW) is associated with impaired focal adhesions (FAs) a disrupted actin cytoskeleton. RANKL production mediated Hedgehog in osteocytes, pathway the primary cilium, ciliary structure tightly coupled Therefore, objective of this study was investigate role cilium EW-mediated osteoclastogenic osteocytes. We report that EW an elongation increase signalling. Significant trends were identified linking cilia reductions cell area % FA area/cell area, indicating disruption FAs contractility. To verify this, we inhibited assembly via ? v ? 3 antagonism contractility demonstrated elongated increased expression Hh markers Rankl expression. our results suggest conditions lead disorganisation integrins reduced contractility, which activation paracrine