Universidad Complutense de Madrid
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High glucose alters the secretome of mechanically stimulated osteocyte-like cells affecting osteoclast precursor recruitment and differentiation

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Maycas, Marta y Portolés Pérez, María Teresa y Matesanz Sancho, María Concepción y Buendía, Irene y Linares, Javier y Feito Castellano, María José y Arcos Navarrete, Daniel y Vallet-Regí, María y Plotkin, Lilian I. y Esbrit, Pedro y Gortázar, Arancha 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). pp. 3611-3621. ISSN 0021-9541, ESSN: 1097-4652

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URL Oficial: http://onlinelibrary.wiley.com/doi/10.1002/jcp.25829/full



Resumen

Diabetes 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) preexposure 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 cellCM. 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.


Tipo de documento:Artículo
Palabras clave:Diabetes mellitus; Mechanotransduction; Osteoclast migration; Osteoclastogenesis; Osteocyte
Materias:Ciencias Biomédicas > Medicina > Fisiología
Ciencias Biomédicas > Biología > Bioquímica
Código ID:44713
Depositado:20 Sep 2017 11:21
Última Modificación:20 Sep 2017 11:48

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