title: Inhibition of osteoclastogenesis by the secretion of osteoprotegerin in vitro by rat dental follicle cells and its implications for tooth eruption.
abstract: Tooth eruption requires the presence of the dental follicle, a loose connective tissue sac that surrounds each unerupted tooth. Early postnatally in the rat, the follicle secretes colony-stimulating factor-1 (CSF-1) and monocyte chemotactic protein-1 (MCP-1), chemotactic molecules that are probably responsible for the recruitment of mononuclear cells. These cells, in turn, fuse to form osteoclasts, which are required for alveolar bone resorption to form an eruption pathway. Recent studies have shown that the osteoprotegerin (OPG) gene is expressed in the dental follicle, but in the first mandibular molar of the rat, that expression is reduced at day 3, the time of maximal osteoclast numbers on the alveolar bone. Inhibition of OPG expression at this time would allow osteoclast formation/activation. To determine if the dental follicle cells do secrete OPG that inhibits osteoclastogenesis, spleen cell cultures were established and soluble osteoclast differentiation factor (ODF) and CSF-1 added to some of them to promote osteoclast formation. In other cultures, dental follicle cells were added in an insert, such that they did not touch the spleen cells. Using a quantitative, tartrate-resistant acid phosphatase (TRAP) assay, it was shown that ODF and CSF-1 promoted osteoclastogenesis in the spleen cell cultures, but the addition of the follicle cells inhibited this and returned the TRAP activities to those seen in cultures of spleen cells only. Adding anti-OPG to these cultures, however, negated the effect of the follicle cells, demonstrating that OPG was the inhibitory molecule secreted by those cells. The follicle cells also immunostained for OPG, confirming that they synthesize OPG. These findings, coupled with those of other studies which show that the periodontal ligament (a derivative of the dental follicle) also secretes OPG, indicate that, except for the period of time in tooth eruption, where osteoclast formation is needed to form an eruption pathway, secretion of OPG would be the norm, presumably to prevent resorption of alveolar bone and subsequent disruption of the periodontal ligament.
authors.affiliation: Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA. gwise@mail.vetmed.lsu.edu
authors.forename: Gary E
authors.initials: GE
authors.lastname: Wise
authors.forename: Shaomian
authors.initials: S
authors.lastname: Yao
authors.forename: Quiyang
authors.initials: Q
authors.lastname: Zhang
authors.forename: Yi
authors.initials: Y
authors.lastname: Ren
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000494:pharmacology; D002478:Cells, Cultured; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003795:Dental Sac / Q000166:cytology / Q000378:metabolism*; D006023:Glycoproteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000494:pharmacology; D010010:Osteoclasts / Q000187:drug effects*; D053244:Osteoprotegerin; D053245:RANK Ligand; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor; D013154:Spleen / Q000166:cytology; D000071681:Tartrate-Resistant Acid Phosphatase; D014078:Tooth Eruption / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; D017077:Culture Media, Conditioned; D006023:Glycoproteins; D007527:Isoenzymes; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C506032:Tnfrsf11b protein, rat; D016173:Macrophage Colony-Stimulating Factor; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase