CCL7 Is a Protective Factor Secreted by Mechanically Loaded Osteocytes
| Autor: | Yukiko Kitase, Lynda F. Bonewald, S. Lee, Mark L. Johnson, Jelica Gluhak-Heinrich, Stephen E. Harris |
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| Rok vydání: | 2014 |
| Předmět: |
endocrine system
Programmed cell death Tooth Movement Techniques Cell Survival medicine.medical_treatment Indomethacin Osteoclasts Protective Agents CCL7 Antibodies Dexamethasone Cell Line Glycogen Synthase Kinase 3 Mice GSK-3 medicine Animals Topoisomerase II Inhibitors Chemokine CCL7 Phosphorylation Autocrine signalling Glucocorticoids General Dentistry Chemokine CCL2 beta Catenin Etoposide Cell Death Tumor Necrosis Factor-alpha Chemistry Anti-Inflammatory Agents Non-Steroidal Research Reports Biomechanical Phenomena Cell biology Mice Inbred C57BL Autocrine Communication medicine.anatomical_structure Cytokine Biochemistry Cell culture Osteocyte Tumor necrosis factor alpha Stress Mechanical Rheology |
| Zdroj: | Journal of Dental Research. 93:1108-1115 |
| ISSN: | 1544-0591 0022-0345 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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