title: Intermittent administration of PTH(1-34) regulates the osteoblastic differentiation of human periodontal ligament cells via protein kinase C- and protein kinase A-dependent pathways in vitro.
abstract: OBJECTIVE
  Intermittent parathyroid hormone (PTH) is recognized as an anabolic agent in regenerative treatment strategies for bony tissues. Periodontal ligament (PDL) cells share features that are typical of osteoblasts, including an osteoblast-like response to stimulation with PTH, which implies a role for these cells in the regulation of repair processes following inflammatory periodontal disease. In the present study we explored the effect of intermittent administration of a PTH fragment [PTH(1-34)] on the osteoblastic differentiation of human PDL cells in vitro, and we investigated the signaling pathways used by the cells to mediate this effect.
  
  
  METHODS
  PDL cells at two stages of confluence were characterized and used as a model for the role of cell maturation in the cellular response.
  
  
  RESULTS
  In preconfluent, less mature cultures, intermittent administration of PTH(1-34) and PTH(1-31) fragments increased alkaline phosphatase (ALP) activity and osteocalcin production, whereas intermittent administration of PTH(3-34) and PTH(7-34) had no effect. RO-32-0432, a specific protein kinase C inhibitor, did not inhibit the PTH(1-34) effect, whereas the protein kinase A inhibitor, H8, antagonized the PTH(1-34)-induced increase in ALP activity and osteocalcin. In contrast, in confluent, more mature cultures, intermittent administration of PTH(1-34), PTH(3-34) and PTH(7-34) fragments, but not of the PTH(1-31) fragment, decreased ALP activity, and osteocalcin and RO-32-0432, but not H8, inhibited the effect.
  
  
  CONCLUSIONS
  This study showed that the PTH(1-34) effect on ALP activity and osteocalcin production in human PDL cells is maturation state-dependent and specific in terms of the pathways involved. Whereas in less mature cells the PTH effect is associated with cyclic AMP/protein kinase A-dependent signaling, more mature cells seem to mediate the PTH signal primarily via protein kinase C-dependent pathways.
authors.affiliation: Department of Orthodontics, Dental Clinic, University of Bonn, Germany. s.lossdoerfer@gmx.de
authors.forename: S
authors.initials: S
authors.lastname: Lossdörfer
authors.forename: D
authors.initials: D
authors.lastname: Kraus
authors.forename: N
authors.initials: N
authors.lastname: Abuduwali
authors.forename: A
authors.initials: A
authors.lastname: Jäger
mesh_terms: D000293:Adolescent; D000469:Alkaline Phosphatase / Q000187:drug effects; D002113:Calcification, Physiologic / Q000187:drug effects; D002452:Cell Count; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects; D002468:Cell Physiological Phenomena; D002648:Child; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005109:Extracellular Matrix / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D010006:Osteoblasts / Q000187:drug effects*; D015675:Osteocalcin / Q000032:analysis; D010281:Parathyroid Hormone / Q000008:administration & dosage; D010446:Peptide Fragments / Q000008:administration & dosage; D010513:Periodontal Ligament / Q000166:cytology / Q000187:drug effects*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000187:drug effects*; D011758:Pyrroles / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D019379:Teriparatide / Q000008:administration & dosage*
chemical_list: D004791:Enzyme Inhibitors; D007211:Indoles; D007546:Isoquinolines; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D011758:Pyrroles; C101312:parathyroid hormone (1-31); C058350:parathyroid hormone (7-34); D015675:Osteocalcin; C063551:parathyroid hormone (3-34)amide; D019379:Teriparatide; C085989:Ro 32-0432; C053177:N-(2-(methylamino)ethyl)-5-isoquinolinesulfonamide; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D000469:Alkaline Phosphatase