CCL7 is a protective factor secreted by mechanically loaded osteocytes

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

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1108-1115
Number of pages8
JournalJournal of Dental Research
Volume93
Issue number11
DOIs
StatePublished - Nov 11 2014
Externally publishedYes

Fingerprint

Osteocytes
Ligands
Cell Death
Dexamethasone
Glycogen Synthase Kinase 3
Tooth Movement Techniques
Catenins
CC Chemokines
Chemotactic Factors
Osteoclasts
Etoposide
Protective Factors
Indomethacin
Glucocorticoids
Tumor Necrosis Factor-alpha
Phosphorylation
Cytokines
Antibodies

Keywords

  • cell death
  • chemokine
  • glucocorticoid
  • mechanical stress
  • TNFα
  • tooth movement

ASJC Scopus subject areas

  • Dentistry(all)
  • Medicine(all)

Cite this

Kitase, Y., Lee, S., Gluhak-Heinrich, J., Johnson, M. L., Harris, S. E., & Bonewald, L. (2014). CCL7 is a protective factor secreted by mechanically loaded osteocytes. Journal of Dental Research, 93(11), 1108-1115. https://doi.org/10.1177/0022034514553008

CCL7 is a protective factor secreted by mechanically loaded osteocytes. / Kitase, Y.; Lee, S.; Gluhak-Heinrich, J.; Johnson, M. L.; Harris, S. E.; Bonewald, Lynda.

In: Journal of Dental Research, Vol. 93, No. 11, 11.11.2014, p. 1108-1115.

Research output: Contribution to journalArticle

Kitase, Y, Lee, S, Gluhak-Heinrich, J, Johnson, ML, Harris, SE & Bonewald, L 2014, 'CCL7 is a protective factor secreted by mechanically loaded osteocytes', Journal of Dental Research, vol. 93, no. 11, pp. 1108-1115. https://doi.org/10.1177/0022034514553008
Kitase, Y. ; Lee, S. ; Gluhak-Heinrich, J. ; Johnson, M. L. ; Harris, S. E. ; Bonewald, Lynda. / CCL7 is a protective factor secreted by mechanically loaded osteocytes. In: Journal of Dental Research. 2014 ; Vol. 93, No. 11. pp. 1108-1115.
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