PTH(1-34)-induced changes in RANKL and OPG expression by human PDL cells modify osteoclast biology in a co-culture model with RAW 264.7 cells

Abstract

Parathyroid hormone (PTH) is widely accepted as an anabolic agent when administered intermittently. Here, we explored the influence of intermittent PTH(1-34) on the expression of local factors by human periodontal ligament (PDL) cells that modify osteoclast biology. This approach aimed at a further elucidation of the role of the hormone and of PDL cells in the regulation of periodontal tissue homeostasis and of repair processes. In a co-culture model of mature PDL cells and RAW 264.7 cells, intermittent PTH(1-34) induced an increased gene expression for tartrate-resistant acid phosphatase (+84%), cathepsin K (+56%), and vitronectin-receptor (+56%); and an enhanced resorptive activity of differentiated osteoclasts (+154%). These findings were correlated with a reduction of the osteoprotegerin (OPG)/receptor activator of nuclear factor kappaB ligand (RANKL) ratio in the presence of PTH(1-34; −44%). Similar results were obtained when RAW cells were cultured with the conditioned medium of PTH(1-34)-stimulated PDL cells. In contrast, when less mature PDL cells were co-cultured with RAW cells, PTH(1-34) induced an inhibition of osteoclastic differentiation (TRAP, −35%; cathepsin K, −28%; vitronectin-receptor, −35%), a reduction of the resorbed substrate area (−77%) and an increase of the OPG/RANKL ratio (+11%). The conditioned medium of PTH(1-34)-pretreated less mature PDL cells led to a down-regulation of the number and activity of multinucleated cells. These data indicate that intermittent PTH(1-34) modifies the expression of membrane-bound and secreted factors by PDL cells which then in turn alter osteoclast biology. The PDL cell response to PTH(1-34) is specific in terms of cell maturation and the mechanism involved.

DOI: 10.1007/s00784-010-0456-0

6 Figures and Tables

0501002011201220132014201520162017
Citations per Year

198 Citations

Semantic Scholar estimates that this publication has 198 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Lossdrfer2010PTH134inducedCI, title={PTH(1-34)-induced changes in RANKL and OPG expression by human PDL cells modify osteoclast biology in a co-culture model with RAW 264.7 cells}, author={Stefan Lossd{\"{o}rfer and Werner Goetz and Andreas J{\"a}ger}, journal={Clinical Oral Investigations}, year={2010}, volume={15}, pages={941-952} }