A macrophage colony-stimulating factor receptor-green fluorescent protein transgene is expressed throughout the mononuclear phagocyte system of the mouse.

Objective. The origin of osteoclasts responsible for bone resorption during orthodontic tooth movement is not yet clear. Their precursors may reside within the periodontal ligament (PDL) or could be recruited from the circulation or the bone marrow. The aim of this study was to investigate the spatial and sequential distribution of osteoclast precursors during experimental tooth movement by using three differentiation markers: receptor for macrophage colony stimulating factor (c-Fms), receptor activator of nuclear factor-κB (RANK), and calcitonin receptor (CTR). Material and Methods. Six-week-old Wistar rats were used. Elastic bands were inserted between the upper 1st and 2nd molars for 1, 2, 3, and 6 days. Immunohistochemical staining for c-Fms, RANK, or CTR was performed on parasagittal sections and positive cells were counted. Results. Before force application, many c-Fms+ and a few RANK+ precursors were present in the bone marrow. No c-Fms+ osteoclast precursors were observed in the PDL. After force a...

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Osteoclast differentiation during experimental tooth movement by a short-term force application: an immunohistochemical study in rats.

The creation of the eruption pathway requires the resorption of the occlusal alveolar bone by osteoclasts and signaling events between bone and dental follicle are necessary. The aim of the present study has been to evaluate the effect of alendronate on osteoclastogenesis and the expression of the regulator proteins of osteoclast activation, namely RANK, RANKL and OPG, in the bone that covers the first molar germ. Newborn Wistar rats were treated daily with 2.5 mg/kg alendronate for 4, 8, 14, 21 and 28 days, whereas controls received sterile saline solution. At the time points cited, maxillae were fixed, decalcified and processed for light and electron microscopic analysis. TRAP histochemistry was performed on semi-serial sections and the osteoclasts in the occlusal half of the bony crypt surface were counted. TUNEL analysis was carried out on paraffin sections. The occlusal bone that covers the upper first molar was removed in additional 4- and 8-day-old alendronate-treated and control rats in which the expression of RANK, RANKL and OPG was analyzed by SDS-polyacrylamide gel electrophoresis and Western blotting. TRAP-positive osteoclasts were more numerous in the alendronate group at all time points, despite their unactivated phenotype and the presence of apoptotic cells. RANKL expression in the alendronate specimens was inhibited at all time points, unlike in controls. Our findings indicate that the expression of RANKL in the occlusal portion of the bony crypt is unrelated to osteoclast recruitment and differentiation but is crucial to their activation during the creation of the eruption pathway.

Reduced RANKL expression impedes osteoclast activation and tooth eruption in alendronate-treated rats

system of the mouse protein transgene is expressed throughout the mononuclear phagocyte green fluorescent - A macrophage colony-stimulating factor receptor

Bone resorption overlying a developing tooth is a necessary event in the creation of an eruption pathway. The formation and function of osteoclasts, which play a major role in bone resorption, are controlled by several factors. Although CSF-1 and its mRNA are expressed in dental follicle cells required for eruption, little is known about the contribution of CSF-1 to osteoclast formation on the bony crypt around the tooth germ. The receptor protein of the CSF-1 encoded proto-oncogene c-fms was identified on multinucleated cells adjacent to the dental follicle, in conjunction with TRAP staining as a marker enzyme for osteoclasts in rat. c-Fms was highly expressed in TRAP-positive multinuclear cells at 3 days postnatal and the number of c-Fms-expressing cells was reduced thereafter. Administration of IL-1alpha, which enhances formation and function of osteoclasts, caused an increase in the number of c-Fms and TRAP-positive cells in rat. On the contrary, injection of calcitonin, which depresses osteoclast formation, caused a decrease in the number. It is obvious that the receptor of CSF-1 is expressed on the surface of osteoclasts around the tooth germ, on the dental follicle. These findings suggested that CSF-1 directly enhances the influx of osteoclasts adjacent to the erupting tooth, resulting in the formation of an eruption pathway.

C A Yoshida

Papers

Expression of CSF-1 receptor on TRAP-positive multinuclear cells around the erupting molars in rats.