Cultured human periodontal ligament cells constitutively express multiple osteotropic cytokines and growth factors, several of which are responsive to mechanical deformation.
OBJECTIVE
A role for cytokines and growth factors in mediating the cellular and molecular events involved in orthodontic tooth movement is well established. The focus to date, however, has been largely on individual mediators, rather than to study cytokines in terms of complex interacting networks. Our objective was to expand our knowledge of the cytokines and growth factors expressed by human periodontal ligament (PDL) cells and to identify new genes that are responsive to mechanical deformation.


METHODS
Human PDL cells were strained with a cyclic deformation of 12% for 6-24 h, and the differential expression of 79 cytokine and growth factor genes was quantified using real-time RT-PCR arrays. For statistical comparison, t-tests were used with mean critical threshold (CT) values derived from triplicate samples.


RESULTS
Forty-one genes were detected at CT values < 35 and, of these, 15 showed a significant change in relative expression. These included seven interleukins (IL): IL1A, IL1F7, IL6 and IL7 (down), IL8, IL11 and IL12A (up). Eight genes representing other cytokine and growth factor families showed comparable mechanical sensitivity, including VEGFD and OPG (down) and PDGFA, INHBA, GDF8 and two transforming growth factor beta genes, TGFB1 and TGFB3 (up). The genes CSF2/GMCSF and IL11 were found to be consistently stimulated across all three time points. Genes that were not expressed included: (1) the immunoregulatory lymphokines (IL2-IL5), IL17 and IL17B; (2) IL10 and other members of the IL-10 family of anti-inflammatory cytokines (IL19, IL20, IL22 and IL24); and (3) TNF and RANKL.


CONCLUSIONS
Human PDL cells constitutively express numerous osteotropic cytokines and growth factors, many of which are mechanoresponsive.
Pinkerton
Mark N
MN
Department of Oral Sciences, Faculty of Dentistry, University of Otago, PO Box 647, Dunedin, New Zealand.
Wescott
David C
DC
Gaffey
Benjamin J
BJ
Beggs
Kyle T
KT
Milne
Trudy J
TJ
Meikle
Murray C
MC
D016723:Bone Remodeling / Q000235:genetics*; D048430:Cell Shape; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D003799:Dental Stress Analysis; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006133:Growth Substances / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D010513:Periodontal Ligament / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013718:Tensile Strength
D016207:Cytokines; D006133:Growth Substances