Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat‑sen University, Guangzhou, Guangdong 510055, P.R. China.
Department of Oral and Maxillofacial Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
Int J Mol Med. 2019 Jun;43(6):2329-2340. doi: 10.3892/ijmm.2019.4171. Epub 2019 Apr 23.
Ameloblastoma is a common odontogenic benign tumor located in the jaws and is characterized by severe local bone destruction. The current study aimed to investigate the effect of interactions between tumor cells and bone marrow stromal cells (BMSCs) on osteoclast formation in ameloblastoma. The impact of ameloblastoma/BMSC interactions on cytokine production, gene expression and osteoclastogenesis was examined using an immortalized ameloblastoma cell line that the authors' previously established. The results demonstrated that interactions between ameloblastoma cells and BMSCs increased interleukin (IL)‑8 and activin A secretion by BMSCs. IL‑8 expression in BMSCs was modulated by tumor‑derived tumor necrosis factor‑α and IL‑8 contributed to osteoclast formation not only directly but also by stimulating receptor activator of NF‑κB ligand (RANKL) expression in BMSCs. Activin A secretion in BMSCs was stimulated by ameloblastoma cells via cell‑to‑cell‑mediated activation of c‑Jun N‑terminal kinase activation, acting as a cofactor of RANKL to induce osteoclast formation and function. The present study highlights the critical role of communication between BMSCs and ameloblastoma cells in bone resorption in ameloblastoma.
成釉细胞瘤是一种常见的牙源性良性肿瘤，位于颌骨内，其特征为严重的局部骨破坏。本研究旨在探讨肿瘤细胞与骨髓基质细胞（BMSCs）之间的相互作用对成釉细胞瘤破骨细胞形成的影响。作者先前建立了一个永生化的成釉细胞瘤细胞系，用于研究成釉细胞瘤/BMSC 相互作用对细胞因子产生、基因表达和破骨细胞形成的影响。结果表明，成釉细胞瘤细胞与 BMSCs 的相互作用增加了 BMSCs 分泌白细胞介素（IL）-8 和激活素 A。肿瘤衍生的肿瘤坏死因子-α调节 BMSCs 中的 IL-8 表达，IL-8 不仅直接促进破骨细胞形成，而且通过刺激 BMSCs 中核因子-κB 受体激活剂配体（RANKL）的表达来促进破骨细胞形成。成釉细胞瘤细胞通过细胞间 c-Jun N-末端激酶激活来刺激 BMSCs 中激活素 A 的分泌，作为 RANKL 的辅助因子诱导破骨细胞形成和功能。本研究强调了 BMSCs 和成釉细胞瘤细胞之间通讯在成釉细胞瘤骨吸收中的关键作用。
