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.
Lossdörfer
Stefan
S
Department of Orthodontics, Dental Clinic, University of Bonn, Welschnonnenstr. 17, 53111 Bonn, Germany. s.lossdoerfer@gmx.de
Götz
Werner
W
Jäger
Andreas
A
D000135:Acid Phosphatase / Q000187:drug effects; D000293:Adolescent; D001862:Bone Resorption / Q000503:physiopathology; D056657:Cathepsin K / Q000187:drug effects; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D002648:Child; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D015536:Down-Regulation; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000187:drug effects; D007527:Isoenzymes / Q000187:drug effects; D010010:Osteoclasts / Q000187:drug effects* / Q000502:physiology; D053244:Osteoprotegerin / Q000187:drug effects*; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010513:Periodontal Ligament / Q000166:cytology / Q000187:drug effects*; D053245:RANK Ligand / Q000187:drug effects*; D012038:Regeneration / Q000187:drug effects; D000071681:Tartrate-Resistant Acid Phosphatase
D017077:Culture Media, Conditioned; D039302:Integrin alphaVbeta3; D007527:Isoenzymes; D053244:Osteoprotegerin; D010281:Parathyroid Hormone; D053245:RANK Ligand; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D056657:Cathepsin K