Major Histocompatibility Complex Class II Transactivator Inhibits Cysteine-rich 61 Expression in Osteoblastic Cells and Its Implication in the Pathogenesis of Periapical Lesions

Introduction: Osteoblastic expression of cysteine-rich 61 (Cyr61) correlates with the severity of periapical lesion associated bone loss, but the regulatory mechanism of Cyr61 expression was not known. Methods: In the study we examined the effect of major histocompatibility complex class II transactivator (CIITA) on tumor necrosis factor (TNF)-alpha-induced Cyr61 synthesis in U2OS human osteoblastic cells by Western blot analysis. In a rat model of bacteria-induced apical periodontitis, we assessed the relation between osteoblastic expressions of CIITA/Cyr61 and disease progression by radiographic and immunohistochemistry studies. Results: We found that forced expression of CIITA suppressed Cyr61 synthesis in U2OS cells. In rat periapical lesions, osteoblastic CIITA decreased as the disease progressed, and expression of CIITA is negatively related to Cyr61 synthesis in osteoblasts. Conclusions: Our data showed that CIITA is a repressor of Cyr61 synthesis in osteoblasts, and it might play a protective role in the pathogenesis of bone resorption in apical periodontitis, possibly through down-regulating the expression of Cyr61 in osteoblasts. (J Endod 2010;36:1021-1025)