Maturation-state dependent response of human periodontal ligament cells to an intermittent parathyroid hormone exposure in vitro.
OBJECTIVE
Parathyroid hormone (parathyroid hormone) has been shown to be capable of exerting anabolic effects on bone when administered intermittently. We hypothesized that parathyroid hormone will modulate the response of periodontal ligament cells in terms of anabolic effects with respect to proliferation, differentiation and the production of key regulatory factors of bone remodeling such as osteoprotegerin and receptor activator of nuclear factor kappaB ligand (RANKL) in a maturation-state dependent manner.


METHODS
Periodontal ligament cells were cultured from human bicuspids obtained from six patients. Following characterization, confluent and preconfluent periodontal ligament cells were challenged with parathyroid hormone (1-34) for 0, 1, 3, 6 or 24 h within three incubation cycles of 48 h each. At harvest, the cell number, alkaline phosphatase specific activity and osteocalcin, osteoprotegerin and RANKL production were determined by means of semiquantitative polymerase chain reaction (PCR) and immunoassays. Dermal fibroblasts and MG63 osteoblast-like cells served as a reference.


RESULTS
Intermittent parathyroid hormone treatment of confluent periodontal ligament cells caused a significant increase in proliferation (+32% maximum) whereas alkaline phosphatase activity, osteocalcin and osteoprotegerin decreased at the transcriptional and translational level (-59.7% maximum). In preconfluent periodontal ligament cells, parathyroid hormone induced a decrease in proliferation (-66.3% maximum) but an increase in differentiation and osteoprotegerin production (+49.2% maximum). RANKL was hardly detectable and unaffected by parathyroid hormone treatment. Similar results were obtained in MG63 cells, whereas parathyroid hormone stimulation did not alter any of the parameters examined in dermal fibroblasts.


CONCLUSIONS
These results indicate that human periodontal ligament cells respond to an intermittent parathyroid hormone exposure with changes in proliferation, differentiation and osteoprotegerin production in a maturation-state dependent manner and therefore might be regulatorily involved in periodontal regeneration.
Lossdörfer
S
S
Department of Orthodontics, Dental Clinic, University of Bonn, Bonn, Germany. s.lossdoerfer@gmx.de
Stier
S
S
Götz
W
W
Jäger
A
A
D000293:Adolescent; D000469:Alkaline Phosphatase / Q000187:drug effects; D016723:Bone Remodeling / Q000187:drug effects; D002352:Carrier Proteins / Q000187:drug effects; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002648:Child; D005347:Fibroblasts / Q000187:drug effects; D006023:Glycoproteins / Q000187:drug effects; D006801:Humans; D008024:Ligands; D008562:Membrane Glycoproteins / Q000187:drug effects; D010006:Osteoblasts / Q000187:drug effects; D015675:Osteocalcin / Q000187:drug effects; D010010:Osteoclasts / Q000187:drug effects; D053244:Osteoprotegerin; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010513:Periodontal Ligament / Q000166:cytology / Q000187:drug effects*; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects; D018124:Receptors, Tumor Necrosis Factor / Q000187:drug effects; D013997:Time Factors; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects
D002352:Carrier Proteins; D006023:Glycoproteins; D008024:Ligands; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D010281:Parathyroid Hormone; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; D014409:Tumor Necrosis Factor-alpha; D015675:Osteocalcin; D000469:Alkaline Phosphatase