Nihon University Graduate School of Dentistry, Nihon, Japan.
J Endod. 2011 Jun;37(6):781-5. doi: 10.1016/j.joen.2011.03.009. Epub 2011 May 6.
The expression of midkine (MK), a heparin-binding growth factor, is increased in various human tumors, making it a promising tumor marker and target for tumor therapy. MK is also related to the regulation of the development and etiology of chronic or autoimmune diseases; however, the involvement of MK in apical periodontitis has never been examined. This study compared the localization of MK-expressing cells and MK messenger RNA expression in periapical granulomas with healthy gingival tissues.
Periapical lesions were removed surgically from chronic apical periodontitis patients, and serial tissue sections were stained with hematoxylin-eosin. The lesions diagnosed as periapical granulomas pathologically were examined by immunohistochemistry using human MK monoclonal antibodies. MK messenger RNA expression was also detected using real-time polymerase chain reaction analysis. Healthy gingival tissues were analyzed in the same manner.
MK was expressed by inflammatory cells, such as macrophages, lymphocytes, and neutrophils, as well as by endothelial cells in periapical granulomas but not in healthy gingival tissues. The MK-expressing inflammatory cells were seen adjacent to blood vessels, which contained MK-expressing endothelial cells, suggesting the interaction of MK among these cells during the process of inflammatory cell infiltration. Quantitative analysis of MK messenger RNA expression revealed that periapical granulomas expressed significantly more MK than healthy gingival tissues.
These findings suggest that MK is involved in the pathogenesis of periapical granulomas.
中期因子（MK）是一种肝素结合生长因子，其在多种人类肿瘤中的表达增加，使其成为有前途的肿瘤标志物和肿瘤治疗靶点。MK 还与慢性或自身免疫性疾病的发展和病因学调节有关；然而，MK 参与根尖周炎的情况尚未被研究过。本研究比较了根尖周肉芽肿中表达 MK 的细胞的定位和 MK 信使 RNA 表达与健康牙龈组织的情况。
从慢性根尖周炎患者中手术切除根尖病变，并对连续的组织切片进行苏木精-伊红染色。通过用人类 MK 单克隆抗体进行免疫组织化学染色，对病理诊断为根尖周肉芽肿的病变进行检查。还使用实时聚合酶链反应分析检测 MK 信使 RNA 表达。以相同的方式分析健康的牙龈组织。
MK 由炎症细胞（如巨噬细胞、淋巴细胞和中性粒细胞）以及根尖周肉芽肿中的内皮细胞表达，但在健康的牙龈组织中不表达。表达 MK 的炎症细胞与含有表达 MK 的内皮细胞的血管相邻，这表明在炎症细胞浸润过程中这些细胞之间存在 MK 的相互作用。MK 信使 RNA 表达的定量分析表明，根尖周肉芽肿中表达的 MK 明显多于健康的牙龈组织。
这些发现表明 MK 参与了根尖周肉芽肿的发病机制。
