Role of osteopontin in the calcification of chronic otitis media

鼓室硬化症是一种导致中耳钙化过程的疾病，通常在中耳慢性炎症后发展。由于骨桥蛋白(OPN)已被证明参与了病理性钙化，我们在此探讨了OPN是否参与了鼓室硬化的钙化过程。取自鼓室硬化症和慢性中耳炎患者的鼓膜和中耳粘膜，根据钙化程度进行组织学分类。在肉眼可见钙化的玻璃化组织和肉眼可见钙化的纤维组织中，钙化灶内也可见OPN，原位杂交证实有大量表达OPN mRNA的细胞位于其周围。OPN和CD68免疫组织化学双重染色显示，表达OPN的细胞呈CD68阳性，提示这些细胞为巨噬细胞。在无钙化的炎性组织中，CD68免疫组织化学和OPN mRNA原位杂交显示大部分表达OPN mRNA的细胞为CD68阳性。逆转录聚合酶链式反应检测炎性组织中OPN基因的表达。提示渗出液巨噬细胞分泌的骨桥蛋白可能是鼓室硬化钙化的重要调节因子。

Tympanosclerosis is a condition leading to a calcification process in the middle ear, and often develops after chronic inflammation of the middle ear. Since osteopontin (OPN) has been shown to participate in the pathological calcification, we here investigated whether OPN is involved in the process of calcification in tympanosclerosis. The tympanic membrane and middle ear mucosa, obtained from patients of tympanosclerosis and chronic otitis media, were histologically classified depending on the calcification degree. In hyalinized tissues with macroscopic calcification and fibrous tissues with microscopic calcification, OPN was also found in the calcifying foci, and many OPN mRNA-expressing cells, determined by in situ hybridization, located around their foci. Moreover, immunohistochemical double staining of OPN and CD68 showed that the OPN-expressing cells were CD68-positive indicating these cells were macrophages. In inflammatory tissues without calcification, immunohistochemistry of CD68 and in situ hybridization of OPN mRNA revealed that most OPN mRNA-expressing cells were CD68-positive. The expression of OPN mRNA in inflammatory tissues was also shown by reverse transcriptase polymerase chain reaction. These results suggested that OPN secreted by exudate macrophages might be an important regulator in the calcification of tympanosclerosis.