title: CD8+ T cells mediate the regenerative PTH effect in hPDL cells via Wnt10b signaling.
abstract: It was the aim of the present investigation to examine whether the stimulating effect of parathyroid hormone (PTH) on human periodontal ligament (hPDL) cell proliferation and differentiation would be enhanced by hPDL/T-cell interaction involving Wnt10b signaling as a mediating pathway. hPDL cells were cultured from healthy premolar tissues of three adolescent orthodontic patients and exposed to PTH(1-34) in monocultures or co-cultures with CD8+T cells. At harvest, proliferation, alkaline phosphatase-specific activity (ALP), and osteocalcin production were determined by immunofluorescence cytochemistry, real-time PCR, biochemical assay, and ELISA. Wnt10b signaling was analyzed by the use of a specific WNT10b neutralizing antibody. PTH(1-34) stimulation of T cells significantly increased Wnt10b expression and production. Wnt10b exposure of hPDL cells enhanced proliferation and differentiation. PDL cells co-cultured with T cells showed a Wnt10b-dependent regulation of proliferation and differentiation parameters. The addition of a Wnt10b-neutralizing Ab to the co-culture medium resulted in a significant inhibition of the PTH(1-34) effect on proliferation, ALP-specific activity, and osteocalcin protein expression. Our findings provide novel insight into the mechanism of action of PTH on hPDL cells and establish the interplay of T cells and hPDL cells via the Wnt10b pathway as a modulating factor for the anabolic properties of the hormone in periodontal regeneration.
authors.affiliation: 1 Department of Orthodontics, University of Bonn, Germany.|2 Department of Orthodontics, University of Jena, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Wolf
authors.affiliation: 1 Department of Orthodontics, University of Bonn, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Lossdörfer
authors.affiliation: 1 Department of Orthodontics, University of Bonn, Germany.
authors.forename: Jana
authors.initials: J
authors.lastname: Marciniak
authors.affiliation: 3 Department of Orthodontics, University of Regensburg, Germany.
authors.forename: Piero
authors.initials: P
authors.lastname: Römer
authors.affiliation: 3 Department of Orthodontics, University of Regensburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Kirschneck
authors.affiliation: 4 Clinic for Pediatric Hematology and Oncology, University of Bonn, Germany.
authors.forename: Rogerio
authors.initials: R
authors.lastname: Craveiro
authors.affiliation: 5 Experimental Dento-Maxillo-Facial Medicine, University of Bonn, Germany.
authors.forename: James
authors.initials: J
authors.lastname: Deschner
authors.affiliation: 1 Department of Orthodontics, University of Bonn, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Jäger
mesh_terms: D000293:Adolescent; D000469:Alkaline Phosphatase / Q000378:metabolism; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002450:Cell Communication; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D002648:Child; D018920:Coculture Techniques; D006801:Humans; D015675:Osteocalcin / Q000378:metabolism; D010281:Parathyroid Hormone / Q000276:immunology; D010513:Periodontal Ligament / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000276:immunology / Q000378:metabolism*; D012038:Regeneration; D015398:Signal Transduction; D051153:Wnt Proteins / Q000276:immunology / Q000378:metabolism*
chemical_list: D057134:Antibodies, Neutralizing; D010281:Parathyroid Hormone; D011518:Proto-Oncogene Proteins; C491119:WNT10B protein, human; D051153:Wnt Proteins; D015675:Osteocalcin; D000469:Alkaline Phosphatase
keywords: Wnt10b; differentiation; hPDL cells; immune cells; interaction; proliferation