CCL7 is a protective factor secreted by mechanically loaded osteocytes

Y. Kitase, S. Lee, J. Gluhak-Heinrich, M. L. Johnson, S. E. Harris, L. F. Bonewald

Producción científica: Articlerevisión exhaustiva

18 Citas (Scopus)

Resumen

In a search for factors up-regulated by mechanical strain in osteocytes, we discovered that chemokine (C-C motif) ligand 7 (CCL7), a chemotactic myokine, was highly expressed in MLO-Y4 osteocyte-like cells. Although MLO-Y4 cells secrete potent chemotactic factors for osteoclast precursors, CCL7 was not responsible for this activity. CCL7 was increased in osteocytes in response to tooth movement in vivo. Since mechanical loading plays a crucial role in maintaining osteocyte viability, CCL7 was tested for protective activity and found to be protective against cell death induced by dexamethasone and etoposide. CCL7 specific antibody partially, but in combination with indomethacin, completely abrogated the protective effects of fluid flow shear stress against dexamethasone-induced cell death. CCL7 activated the β-catenin pathway through phosphorylation of glycogen synthase kinase 3 (GSK-3), suggesting that this pathway is responsible for the observed protective effects. A related cytokine, CCL2, also produced by MLO-Y4 cells but not regulated by mechanical loading, proved to be more potent and protected against cell death induced by not only dexamethasone, but also by Tumor Necrosis Factor α (TNFα). Whereas osteocytes may produce CCL2 in constitutively low levels, a major function of mechanically induced CCL7 may be to selectively protect osteocytes in an autocrine manner against glucocorticoid-induced cell death.

Idioma originalEnglish (US)
Páginas (desde-hasta)1108-1115
Número de páginas8
PublicaciónJournal of dental research
Volumen93
N.º11
DOI
EstadoPublished - nov 11 2014

ASJC Scopus subject areas

  • General Dentistry

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