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 DPSC-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-B 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.
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