Maturation‐state dependent response of human periodontal ligament cells to an intermittent parathyroid hormone exposure in vitro

Abstract

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. 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. 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. 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.