Preventive Effects of Dental Pulp Stem Cell-conditioned Media on Anti-RANKL Antibody-Related Osteonecrosis of the Jaw

Calcif Tissue Int. 2024 Aug;115(2):185-195. doi: 10.1007/s00223-024-01232-1. Epub 2024 May 29.

Abstract

Medication-related osteonecrosis of the jaw is a serious disease occurring in patients with cancer and osteoporosis, who are undergoing treatment with antiresorptive agents (ARAs) such as bisphosphonate (BP) or denosumab, an antibody targeting receptor activator of NF-κB ligand. Recently, stem cell-based therapy has been shown to be effective in preventing the development of bisphosphonate-related osteonecrosis of the jaw. However, studies on denosumab-related osteonecrosis of the jaw (DRONJ) remain limited. Here, the efficacy of treatment with dental pulp stem cell conditioned media (DPSC-CM) in preventing DRONJ in a murine model was evaluated. Local administration of DPSC-CM into the extraction socket of a mouse with DRONJ decreased the number of empty osteocyte lacunae and the prevalence of ONJ. In tissues surrounding the extraction sockets in the DPSC-CM-treated group, the expression of inflammatory cytokines was attenuated and that of osteogenesis-related molecules was enhanced compared to that in the control group. Further, the expression of Wnt signaling molecules, which had been suppressed, was improved. These findings collectively suggest that DPSC-CM prevents ONJ development in a murine DRONJ model.

Keywords: Anti-RANKL antibody; Denosumab-related osteonecrosis of the jaw; Dental pulp stem cell conditioned media; Medication-related osteonecrosis of the jaw.

MeSH terms

  • Animals
  • Bisphosphonate-Associated Osteonecrosis of the Jaw* / prevention & control
  • Culture Media, Conditioned / pharmacology
  • Denosumab* / pharmacology
  • Dental Pulp* / drug effects
  • Disease Models, Animal
  • Humans
  • Male
  • Mice
  • Osteogenesis / drug effects
  • RANK Ligand* / metabolism
  • Stem Cells* / drug effects

Substances

  • Culture Media, Conditioned
  • Denosumab
  • RANK Ligand