title: Parathyroid hormone-related protein induces spontaneous osteoclast formation via a paracrine cascade.
abstract: Experiments in vivo have established that tooth eruption fails in the absence of parathyroid hormone (PTH)-related protein (PTHrP) action in the microenvironment of the tooth because of the failure of osteoclastic bone resorption on the coronal tooth surface to form an eruption pathway. To elucidate the effects of PTHrP on osteoclast regulation in this environment, we established primary cultures of epithelial stellate reticulum cells and mesenchymal dental follicle (DF) cells surrounding the teeth. When cocultured, these cells are fully capable of supporting the formation of functional osteoclasts in the absence of added splenic osteoclast precursors, osteoblasts, or vitamin D/PTH/PTHrP. Neutralizing the effects of PTHrP resulted in a decrease in the number of osteoclasts formed, suggesting that stellate reticulum-derived PTHrP drives osteoclast formation. DF cells were found to express functional PTH/PTHrP type I receptors, and conditioned media collected from PTHrP-treated DF cells were able to induce bone resorption in the fetal-rat long-bone assay. PTHrP treatment also induced an increase in osteoclast differentiation factor expression and a concomitant decrease in osteoclastogenesis inhibitory factor expression in DF cells. The addition of osteoclastogenesis inhibitory factor resulted in a decrease in the number of osteoclasts formed in the cocultures, suggesting that osteoclast formation is mediated by osteoclast differentiation factor. Thus, PTHrP seems to regulate osteoclast formation via mediation of the DF, in a manner analogous to the osteoblast-mediated process in the peripheral skeleton. The primary coculture system of dental crypt cells also offers a system for the study of osteoclast formation and regulation.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: I A
authors.initials: IA
authors.lastname: Nakchbandi
authors.forename: E E
authors.initials: EE
authors.lastname: Weir
authors.forename: K L
authors.initials: KL
authors.lastname: Insogna
authors.forename: W M
authors.initials: WM
authors.lastname: Philbrick
authors.forename: A E
authors.initials: AE
authors.lastname: Broadus
mesh_terms: D000818:Animals; D002450:Cell Communication; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003795:Dental Sac / Q000166:cytology / Q000502:physiology; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D010010:Osteoclasts / Q000166:cytology* / Q000502:physiology*; D019899:Paracrine Communication; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins / Q000502:physiology*
chemical_list: D044162:Parathyroid Hormone-Related Protein; D011506:Proteins