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

• Published in: Calcified tissue international Vol. 115; no. 2; pp. 185 - 195
• Main Authors: Kaminogo, Kento, Yamaguchi, Satoshi, Chen, Hui, Yagita, Hideo, Toyama, Naoto, Urata, Yusuke, Hibi, Hideharu
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.08.2024; Springer Nature B.V
• Subjects: Animal models; Biochemistry; Biomedical and Life Sciences; Bisphosphonates; Cell Biology; Dental pulp; Endocrinology; Jaw; Life Sciences; Necrosis; NF-κB protein; Original Research; Orthopedics; Osteogenesis; Osteonecrosis; Osteoporosis; Stem cells; Wnt protein; Dental pulp stem cell conditioned media; Medication-related osteonecrosis of the jaw; Anti-RANKL antibody; Denosumab-related osteonecrosis of the jaw
• ISSN: 1432-0827; 0171-967X; 1432-0827
• DOI: 10.1007/s00223-024-01232-1

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.