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

Abstract

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.

DC-STAMP: A Key Regulator in Osteoclast Differentiation

“…Teeth are part of the skeletal system where active bone remodeling constantly occurs. Osteoclasts are involved in tooth development especially during the stage of tooth eruption (Bradaschia‐Correa et al, ). Together with other cell subsets and cytokine profiles present at local tooth areas, osteoclasts play an important role in the pathogenesis of periodontal diseases (Garlet et al, ; Jager et al, ; Bradaschia‐Correa et al, ; Kondo et al, ).…”

“…Osteoclasts are involved in tooth development especially during the stage of tooth eruption (Bradaschia‐Correa et al, ). Together with other cell subsets and cytokine profiles present at local tooth areas, osteoclasts play an important role in the pathogenesis of periodontal diseases (Garlet et al, ; Jager et al, ; Bradaschia‐Correa et al, ; Kondo et al, ). A possible involvement of DC‐STAMP in tooth development is suggested by an increased rate of tooth malocclusion in DC‐STAMP KO mice, a phenotype which is closely linked to the homozygous DC‐STAMP−/− loci (unpublished data, manuscript submitted).…”

“…The malocclusion phenotype of DC‐STAMP KO was discovered unexpectedly due to a frequent diet‐uptake problem reported from our animal facility. More studies will be necessary to investigate the role of DC‐STAMP in teeth development in the context of local cytokine profile including RANKL (Bradaschia‐Correa et al, ) receptors, and physiological inhibitors and growth factors during peridontal disease progression and tooth eruption.…”

Ultrastructural and immunohistochemical study of the effect of sodium alendronate in the progression of experimental periodontitis in rats

“…The exact mechanism of such drugs in the osteoclast metabolism is not completely known, but it culminates in the inhibition of the cell attachment to the mineralized matrix and development of the resorption apparatus such as the ruffled border and clear zone (Bradaschia‐Correa et al, ). ALN was demonstrated to inhibit the expression of RANKL during the resorption of the alveolar crest in tooth eruption, impeding the activation of osteoclasts, which presented latent phenotype (Bradaschia‐Correa et al, ). The expression of RANKL by marrow cells from human patients taking ALN was reduced in vitro (Eslami et al, ).…”

Effects of Bisphosphonate on the Expression of Matrix Enzymes during Endochondral Ossification

“…Furthermore, they can reduce cell proliferation, induce apoptosis of tumor cells and inhibit adhesion and invasion of tumor cell into the extracellular matrix in vitro [4,5]. Thus, clinical applications have been attempted for the treatment of bone diseases, such as osteoporosis and Paget disease, prevention of metastasis of tumor cells to bone [6] and prevention of alveolar bone resorption after tooth extraction [7,8].…”