Origins of Alterations to Rankl Null Mutant Mouse Dental Root Development

Abstract

The purpose of the present study was to assess the early stages of development of mouse first molar roots in the osteopetrotic context of RANKL invalidation in order to demonstrate that the radicular phenotype observed resulted not only from defective osteoclasts, but also from loss of cell-to-cell communication among dental, periodontium and alveolar bone cells involving RANKL signaling. Two experimental models were used in this study: Rankl mutants with permanent RANKL invalidation, and C57BL/6J mice injected during the first postnatal week with a RANKL neutralizing antibody corresponding to a transient RANKL invalidation. The dento-alveolar complex was systematically analyzed using micro-CT, and histological and immunohistochemical approaches. These experiments showed that the root elongation alterations observed in the Rankl-/- mice were associated with reduced proliferation of the RANK-expressing HERS cells with a significant decrease in proliferating cell nuclear antigen (PCNA) expression and a significant increase in P21 expression. The phenotypic comparison of the adult first molar root at 35 days between permanent and transitory invalidations of RANKL made it possible to demonstrate that alterations in dental root development have at least two origins, one intrinsic and linked to proliferation/differentiation perturbations in dental-root-forming cells, the other extrinsic and corresponding to disturbances of bone cell differentiation/function.

The Role of GH/IGF Axis in Dento-Alveolar Complex from Development to Aging and Therapeutics: A Narrative Review

“…During bone formation, growth factors (including IGF1) released from the bone matrix during osteoclastic bone resorption stimulate osteoblast differentiation, thus bone remodeling. Molar root formation and tooth eruption are dependent on both (anabolic) osteoblast and (catabolic) osteoclast activities controlled by receptor activator of NF-κB ligand (RANKL) as demonstrated in RANKL -/- mice [ 55 , 56 ]. In these mutants, the IGF signaling pathway is down-regulated in cells involved in root elongation and this impairment is rescued by the addition of IGF1, demonstrating that dental root and eruption defect in RANKL mutant mice may result from failure of IGF1 release from bone matrix through osteoclast bone resorption.…”

Maxillary and dental development in the offspring of protein‐restricted female rats

“…The RANKL/OPG system was analyzed due to the versatility of RANKL as a paracrine molecule acting as a receptor or being released into matrix [21,22]. Dental pulp cells and odontoblasts express RANKL and OPG [6,20,56], but their function during odontogenesis has not been well described. Under physiological conditions, the RANKL/OPG ratio in dental pulp environment was lower [57]; however, during pulp damages, its ratio expression enhanced and stimulated odontoclastogenesis [58].…”

“…Recent studies demonstrate a pivotal role played by the RANKL (receptor activator of nuclear factor-kappa beta ligand) and OPG (osteoprotegerin) system during dentinogenesis [6,20,21]. Moreover, the tooth-eruption process requires activation and recruitment of osteoclasts on the alveolar bone surface developing an eruption pathway regulated by the RANKL/OPG system [22,23].…”