title: Gingival fibroblasts are better at inhibiting osteoclast formation than periodontal ligament fibroblasts.
abstract: Various studies indicate that periodontal ligament fibroblasts (PLF) have some similarities to osteoblasts, for example they have the capacity to induce the formation of osteoclast-like cells. Here, we investigated whether a second population of tooth-associated fibroblasts, gingival fibroblasts (GF), has similar osteoclastogenesis properties. PLF and GF were co-cultured with peripheral blood mononuclear cells (PBMC) in the presence and absence of dexamethasone and 1alpha,25dihydroxycholecalciferol (dex + vit D(3)) on plastic and on cortical bone slices. Tartrate resistant acid phosphatase (TRACP) positive multinucleated cells (MNCs) were more abundant in co-cultures with PLF than in GF-PBMC co-cultures, more abundant on plastic compared to bone and more abundant in the presence of dex + vit D(3). In line with these findings was an inhibition of MNC formation and not inhibition of existing osteoclasts by medium conditioned by GF. We next investigated whether expression of molecules important for osteoclastogenesis differed between the two types of fibroblasts and whether these molecules were regulated by dex + vit D(3). OPG was detected at high levels in both fibroblast cultures, whereas RANKL could not be detected. Resorption of bone did not occur by the MNCs formed in the presence of either fibroblast subpopulation, suggesting that the fibroblasts secrete inhibitors of bone resorption or that the osteoclast-like cells were not functional. The incapacity of the MNCs to resorb was abolished by culturing the fibroblast-PBMC cultures with M-CSF and RANKL. Our results suggest that tooth-associated fibroblasts may trigger the formation of osteoclast-like cells, but more importantly, they play a role in preventing bone resorption, since additional stimuli are required for the formation of active osteoclasts.
authors.affiliation: Department of Experimental Periodontology, Universiteit van Amsterdam and Vrije Universiteit, The Netherlands.
authors.forename: Teun J
authors.initials: TJ
authors.lastname: de Vries
authors.forename: Ton
authors.initials: T
authors.lastname: Schoenmaker
authors.forename: Nutthamon
authors.initials: N
authors.lastname: Wattanaroonwong
authors.forename: Marije
authors.initials: M
authors.lastname: van den Hoonaard
authors.forename: Arlies
authors.initials: A
authors.lastname: Nieuwenhuijse
authors.forename: Wouter
authors.initials: W
authors.lastname: Beertsen
authors.forename: Vincent
authors.initials: V
authors.lastname: Everts
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D000328:Adult; D001862:Bone Resorption / Q000503:physiopathology / Q000517:prevention & control; D002352:Carrier Proteins / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D018920:Coculture Techniques / Q000379:methods; D003907:Dexamethasone / Q000494:pharmacology; D005347:Fibroblasts / Q000502:physiology*; D005434:Flow Cytometry / Q000379:methods; D005881:Gingiva / Q000166:cytology*; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology* / Q000378:metabolism; D010014:Osteolysis / Q000503:physiopathology; D010513:Periodontal Ligament / Q000166:cytology*; D010519:Periodontium / Q000166:cytology; D016133:Polymerase Chain Reaction / Q000379:methods; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology*; D000071681:Tartrate-Resistant Acid Phosphatase; D014070:Tooth
chemical_list: D002352:Carrier Proteins; D006023:Glycoproteins; D007527:Isoenzymes; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human; D003907:Dexamethasone; D016173:Macrophage Colony-Stimulating Factor; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase