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


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

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@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} }