Kim Minah, Choi Minji, Kwon Yong-Dae, Ohe Joo-Young, Jung Junho
Department of Oral & Maxillofacial Surgery, Kyung Hee University College of Dentistry, Kyung Hee University Medical Center, Seoul 02447, Republic of Korea.
Division of Oral & Maxillofacial Surgery, Department of Dentistry, Saint Vincent's Hospital, The Catholic University of Korea, Suwon 16247, Republic of Korea.
Life (Basel). 2024 Aug 29;14(9):1088. doi: 10.3390/life14091088.
The suppressive effect of bisphosphonates (BPs) on bone metabolism is considered to be a major cause of medication-related osteonecrosis of the jaw (MRONJ). Enamel matrix derivative (EMD) stimulates and activates growth factors, leading to the regeneration of periodontal tissues. In this study, we aimed to explore the potential of EMD in reversing the detrimental effects of BPs on human fetal osteoblasts (hFOBs) and osteosarcoma-derived immature osteoblasts (MG63s) by assessing cell viability, apoptosis, migration, gene expression, and protein synthesis. While the suppressive effect of zoledronate (Zol) on cell viability and migration was observed, the addition of EMD significantly mitigated this effect and enhanced cell viability and migration. Furthermore, an increased apoptosis rate induced by Zol was decreased with the addition of EMD. The decreased gene expression of alkaline phosphatase (ALP), osteocalcin (OC), and the receptor activator of nuclear factors kappa-B ligand (RANKL) caused by BP treatment was reversed by the co-addition of EMD to hFOB cells. This trend was also observed for ALP and bone sialoprotein (BSP) levels in MG63 cells. Furthermore, suppressed protein levels of OC, macrophage colony-stimulating factor (M-CSF), BSP, and type 1 collagen (COL1) were recovered following the addition of EMD. This finding suggests that EMD could mitigate the effects of BPs, resulting in the recovery of cell survival, migration, and gene and protein expression. However, the behavior of the osteoblasts was not fully restored, and further studies are necessary to confirm their effects at the cellular level and to assess their clinical usefulness in vivo for the prevention and treatment of MRONJ.
双膦酸盐（BPs）对骨代谢的抑制作用被认为是药物相关性颌骨坏死（MRONJ）的主要原因。釉基质衍生物（EMD）可刺激并激活生长因子，从而促进牙周组织再生。在本研究中，我们旨在通过评估细胞活力、凋亡、迁移、基因表达和蛋白质合成，探索EMD逆转BPs对人胎儿成骨细胞（hFOBs）和骨肉瘤来源的未成熟成骨细胞（MG63s）有害影响的潜力。虽然观察到唑来膦酸（Zol）对细胞活力和迁移有抑制作用，但添加EMD可显著减轻这种作用并增强细胞活力和迁移能力。此外，添加EMD可降低Zol诱导的凋亡率。通过向hFOB细胞中共同添加EMD，可逆转BP处理导致的碱性磷酸酶（ALP）、骨钙素（OC）和核因子κB受体激活剂配体（RANKL）基因表达的降低。在MG63细胞中，ALP和骨唾液蛋白（BSP）水平也观察到了这种趋势。此外，添加EMD后，OC、巨噬细胞集落刺激因子（M-CSF）、BSP和I型胶原（COL1）的蛋白水平受到的抑制得以恢复。这一发现表明，EMD可减轻BPs的影响，从而使细胞存活、迁移以及基因和蛋白质表达得以恢复。然而，成骨细胞的行为并未完全恢复，有必要进一步研究以确认其在细胞水平的作用，并评估其在体内预防和治疗MRONJ的临床实用性。
