PMID- 25274752
OWN - NLM
STAT- MEDLINE
DCOM- 20141218
LR  - 20211021
IS  - 1544-0591 (Electronic)
IS  - 0022-0345 (Print)
IS  - 0022-0345 (Linking)
VI  - 93
IP  - 11
DP  - 2014 Nov
TI  - CCL7 is a protective factor secreted by mechanically loaded osteocytes.
PG  - 1108-15
LID - 10.1177/0022034514553008 [doi]
AB  - 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 beta-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 alpha (TNFalpha). 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.
CI  - (c) International & American Associations for Dental Research.
FAU - Kitase, Y
AU  - Kitase Y
AD  - Oral and Craniofacial Sciences, School of Dentistry, University of 
      Missouri-Kansas City, Kansas City, MO, USA kitasey@umkc.edu.
FAU - Lee, S
AU  - Lee S
AD  - Endocrinology, Internal Medicine, Eulji University School of Medicine, Daejeon 
      City, Republic of Korea.
FAU - Gluhak-Heinrich, J
AU  - Gluhak-Heinrich J
AD  - Orthodontics.
FAU - Johnson, M L
AU  - Johnson ML
AD  - Oral and Craniofacial Sciences, School of Dentistry, University of 
      Missouri-Kansas City, Kansas City, MO, USA.
FAU - Harris, S E
AU  - Harris SE
AD  - Periodontics and Cellular and Structural Biology, University of Texas Health 
      Science Center at San Antonio, San Antonio, TX, USA.
FAU - Bonewald, L F
AU  - Bonewald LF
AD  - Oral and Craniofacial Sciences, School of Dentistry, University of 
      Missouri-Kansas City, Kansas City, MO, USA.
LA  - eng
GR  - P01 AR046798/AR/NIAMS NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20141001
PL  - United States
TA  - J Dent Res
JT  - Journal of dental research
JID - 0354343
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Antibodies)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Ccl7 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CCL7)
RN  - 0 (Glucocorticoids)
RN  - 0 (Protective Agents)
RN  - 0 (Topoisomerase II Inhibitors)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (beta Catenin)
RN  - 6PLQ3CP4P3 (Etoposide)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
RN  - XXE1CET956 (Indomethacin)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents, Non-Steroidal/pharmacology
MH  - Antibodies/pharmacology
MH  - Autocrine Communication/physiology
MH  - Biomechanical Phenomena
MH  - Cell Death/drug effects
MH  - Cell Line
MH  - Cell Survival/physiology
MH  - Chemokine CCL2/metabolism
MH  - Chemokine CCL7/immunology/*metabolism
MH  - Dexamethasone/pharmacology
MH  - Etoposide/pharmacology
MH  - Glucocorticoids/pharmacology
MH  - Glycogen Synthase Kinase 3/drug effects
MH  - Indomethacin/pharmacology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Osteoclasts/*metabolism
MH  - Phosphorylation
MH  - Protective Agents/*metabolism
MH  - Rheology
MH  - Stress, Mechanical
MH  - Tooth Movement Techniques/instrumentation
MH  - Topoisomerase II Inhibitors/pharmacology
MH  - Tumor Necrosis Factor-alpha/pharmacology
MH  - beta Catenin/drug effects
PMC - PMC4212466
OTO - NOTNLM
OT  - TNFalpha
OT  - cell death
OT  - chemokine
OT  - glucocorticoid
OT  - mechanical stress
OT  - tooth movement
COIS- The authors declare no potential conflicts of interest with respect to the 
      authorship and/or publication of this article.
EDAT- 2014/10/03 06:00
MHDA- 2014/12/19 06:00
PMCR- 2015/11/01
CRDT- 2014/10/03 06:00
PHST- 2014/10/03 06:00 [entrez]
PHST- 2014/10/03 06:00 [pubmed]
PHST- 2014/12/19 06:00 [medline]
PHST- 2015/11/01 00:00 [pmc-release]
AID - 0022034514553008 [pii]
AID - 10.1177_0022034514553008 [pii]
AID - 10.1177/0022034514553008 [doi]
PST - ppublish
SO  - J Dent Res. 2014 Nov;93(11):1108-15. doi: 10.1177/0022034514553008. Epub 2014 Oct 
      1.