RANKL/OPG ratio regulates odontoclastogenesis in damaged dental pulp

Sci Rep. 2021 Feb 25;11(1):4575. doi: 10.1038/s41598-021-84354-y.

Abstract

Bone-resorbing osteoclasts are regulated by the relative ratio of the differentiation factor, receptor activator NF-kappa B ligand (RANKL) and its decoy receptor, osteoprotegerin (OPG). Dental tissue-localized-resorbing cells called odontoclasts have regulatory factors considered as identical to those of osteoclasts; however, it is still unclear whether the RANKL/OPG ratio is a key factor for odontoclast regulation in dental pulp. Here, we showed that odontoclast regulators, macrophage colony-stimulating factor-1, RANKL, and OPG were detectable in mouse pulp of molars, but OPG was dominantly expressed. High OPG expression was expected to have a negative regulatory effect on odontoclastogenesis; however, odontoclasts were not detected in the dental pulp of OPG-deficient (KO) mice. In contrast, damage induced odontoclast-like cells were seen in wild-type pulp tissues, with their number significantly increased in OPG-KO mice. Relative ratio of RANKL/OPG in the damaged pulp was significantly higher than in undamaged control pulp. Pulp damages enhanced hypoxia inducible factor-1α and -2α, reported to increase RANKL or decrease OPG. These results reveal that the relative ratio of RANKL/OPG is significant to pulpal odontoclastogenesis, and that OPG expression is not required for maintenance of pulp homeostasis, but protects pulp from odontoclastogenesis caused by damages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers
  • Cell Differentiation
  • Cellular Microenvironment / genetics
  • Dental Pulp / metabolism*
  • Dental Pulp / pathology
  • Fluorescent Antibody Technique / methods
  • Gene Expression
  • Immunohistochemistry
  • Mice
  • Models, Biological
  • Odontogenesis* / genetics
  • Osteoclasts / metabolism*
  • Osteoprotegerin / metabolism*
  • RANK Ligand / metabolism*

Substances

  • Biomarkers
  • Osteoprotegerin
  • RANK Ligand
  • Tnfrsf11b protein, mouse