Investigation on the Action and Effect of Culture Supernatant of Human Dental Pulp Stem Cells Using Rats with Medication-Related Osteonecrosis of the Jaw

Abstract

The incidence of osteonecrosis of the jaw (ONJ) in association with bisphosphonate (BP) preparations (medication-related ONJ, MRONJ) has reportedly increased rapidly in the recent times. Despite the increase, specific cure remains to be established. In this study, MRONJ model rats were constructed, the action and effect of dental pulp stem cell-conditioned medium (DPSC-CM) on MRONJ were evaluated. Following BP preparation (sodium zoledronate, ZOL) administration to rats via the jugular vein, the first molar of the right maxilla was extracted to obtain MRONJ model rats, which served as the control group. Model rats were further administered with either Dulbecco Modified Eagle Medium (DMEM) or DP-SC-CM via the jugular vein. These groups were comparatively analyzed, and the jawbone at the site of dental extraction was used as the test sample. Compared with control group and DMEM group, the DPSC-CM group exhibited unique macroscopic findings characterized by the narrowed width of bone exposure and increased mucous coating. Histological analysis revealed a significant decrease in the number of hollow bone lacunae, implying improved osteonecrosis. In immunohistological studies, it was discerned that ZOL administration promoted osteoprotegerin (OPG) production in the osteoblasts and suppressed the synthesis of receptor activator of nuclear factor kappa-Β ligand (RANKL). Conversely, the DPSC-CM group displayed suppressed OPG and accelerated RANKL expressions, with an increase in the number of vascular endothelial growth factor-positive cells. Furthermore, Tartrate-resistant acid phosphatase/alkaline phosphatase (TRAP/ALP) staining suggested improved bone remodeling capability in this group. Thus, DPSC-CM administration improves ischemic osteonecrosis and may, therefore, be an effective therapeutic option.

Regeneration of Dentin Using Stem Cells Present in the Pulp

“…It is well known that the pulp is rich in adult mesenchymal stem cells (MSCs), and the stem cells isolated from the pulp have high proliferative potential and may be able to differentiate into hard tissueforming cells. Additionally, dental pulp stem cells play an important role in regenerative medicine for both oral and non-oral areas because of their high proliferation rate, pluripotency, and ease of collection [47]. Therefore, pulp stem cells are a promising source of MSCs used in a variety of clinical applications, such as bone formation, tooth tissue engineering, and nerve tissue regeneration [48].…”

Geometrical Structure of Honeycomb TCP to Control Dental Pulp-Derived Cell Differentiation

“…Dental pulp is well known to be enriched with adult mesenchymal stem cells (MSCs), and stem cells isolated from dental pulp have high proliferation ability and might be able to differentiate into dentin-forming osteoblasts [ 1 , 2 , 3 ]. In addition, dental pulp stem cells play an important role in regenerative medicine, both for oral and non-oral region pathologies due to their high proliferation rates, multipotency, and accessibility [ 4 , 5 ]. Thus, dental pulp stem cells are a promising source of multipotent MSCs used in various clinical applications such as bone formation, dental tissue engineering, and the regeneration of neural tissue [ 6 , 7 , 8 , 9 ].…”