Parathyroid hormone-related protein induces spontaneous osteoclast formation via a paracrine cascade

Experiments in vivo have established that tooth eruption fails in the absen ce of parathyroid hormone (PTH)-related protein (PTHrP) action in the micro environment of the tooth because of the failure of osteoclastic bone resorp tion on the coronal tooth surface to form an eruption pathway. To elucidate the effects of PTHrP on osteoclast regulation in this environment, we esta blished primary cultures of epithelial stellate reticulum cells and mesench ymal dental follicle (DF) cells surrounding the teeth. When cocultured. the se cells are fully capable of supporting the formation of functional osteoc lasts in the absence of added splenic osteoclast precursors, osteoblasts. o r vitamin D/PTH/PTHrP, Neutralizing the effects of PTHrP resulted in a decr ease in the number of osteoclasts formed, suggesting that stellate reticulu m-derived PTHrP drives osteoclast formation. DF cells were found to express functional PTH/PTHrP type I receptors, and conditioned media collected fro m PTHrP-treated DF cells were able to induce bone resorption in the fetal-r at long-bone assay. PTHrP treatment also induced an increase in osteoclast differentiation factor expression and a concomitant decrease in osteoclasto genesis inhibitory factor expression in or cells. The addition of osteoclas togenesis inhibitory factor resulted in a decrease in the number of osteocl asts formed in the cocultures. suggesting that osteoclast formation is medi ated by osteoclast differentiation factor. Thus, PTHrP seems to regulate os teoclast formation via mediation of the DF, in a manner analogous to the os teoblast-mediated process in the peripheral skeleton. The primary coculture system of dental crypt cells also offers a system for the study of osteocl ast formation and regulation.