Maycas, MartaPortolés, Maria TeresaMatesanz, María ConcepciónBuendía, IreneLinares, JavierFeito, María JoséArcos, DanielVallet-Regí, MaríaPlotkin, LilianEsbrit, PedroGortázar, Arancha R.2018-01-052018-01-052017-12Maycas, M., Portolés, M. T., Matesanz, M. C., Buendía, I., Linares, J., Feito, M. J., … Gortázar, A. R. (2017). High glucose alters the secretome of mechanically stimulated osteocyte‐like cells affecting osteoclast precursor recruitment and differentiation. Journal of Cellular Physiology, 232(12), 3611–3621. https://doi.org/10.1002/jcp.25829https://hdl.handle.net/1805/14947Diabetes mellitus (DM) induces bone deterioration, while mechanical stimulation promotes osteocyte-driven bone formation. We aimed to evaluate the interaction of acute exposure (24 h) to high glucose (HG) with both the pro-survival effect conferred to osteocytic MLO-Y4 cells and osteoblastic MC3T3-E1 cells by mechanical stimulation and the interaction of these cells with osteoclast precursor RAW264.7 cells. We found that 24 h of HG (25 mM) pre-exposure prevented both cell survival and ERK and β-catenin nuclear translocation upon mechanical stimulation by fluid flow (FF) (10 min) in both MLO-Y4 and MC3T3-E1 cells. However, migration of RAW 264.7 cells was inhibited by MLO-Y4 cell-conditioned medium (CM), but not by MC3T3-E1 cell-CM, with HG or FF. This inhibitory effect was associated with consistent changes in VEGF, RANTES, MIP-1α, MIP-1β MCP-1, and GM-CSF in MLO-Y4 cell-CM. RAW264.7 proliferation was inhibited by MLO-Y4 CM under static or HG conditions, but it increased by FF-CM with or without HG. In addition, both FF and HG abrogated the capacity of RAW 264.7 cells to differentiate into osteoclasts, but in a different manner. Thus, HG-CM in static condition allowed formation of osteoclast-like cells, which were unable to resorb hydroxyapatite. In contrast, FF-CM prevented osteoclastogenesis even in HG condition. Moreover, HG did not affect basal RANKL or IL-6 secretion or their inhibition induced by FF in MLO-Y4 cells. In conclusion, this in vitro study demonstrates that HG exerts disparate effects on osteocyte mechanotransduction, and provides a novel mechanism by which DM disturbs skeletal metabolism through altered osteocyte-osteoclast communication.enPublisher Policydiabetes mellitusmechanotransductionosteocyteArticle