钙化是多种心包疾病进展和自体心包修复材料衰败的关键事件，而最新研究表明用破骨细胞吸收组织中沉积的钙是诱导异位钙化消退的一个潜在通路，但遗憾的是钙化心包缺少破骨细胞。鉴于巨噬细胞在钙化心包中分布的普遍性以及与破骨细胞起源的相近性，我们设想采用细胞表型转录因子将心包中的巨噬细胞原位转分化为破骨细胞将是增加其细胞数量的新策略。前期，我们已证实敲除C/EBPα的同时、增加MITF-E的表达（CM）可启闭巨噬细胞和破骨细胞之间的表型开关。因而我们拟以此为契机，旨在进一步分析CM启动和维持巨噬细胞和破骨细胞表型转换的分子信号调控机制；同时，构建体外和体内心包钙化模型，采用巨噬细胞特异性启动子实现CM在巨噬细胞中的特异表达，观察转分化的破骨细胞对钙盐的吸收能力。通过此研究，力图阐明CM作用机制，明确原位转分化破骨细胞消退心包钙化的可行性，并为其它钙化性疾病的防治提供理论依据。

Calcification is the key event contributing to the progression of a variety of pericardial diseases and degeneration of autologous pericardial repair materials. Recent studies have suggested that osteoclastic calcium resorption is a potential pathway to induce ectopic calcification regression, but unfortunately, the lack of osteoclasts in calcified pericardia restricts the application of this procedure. Given that calcified areas are surrounded by an abundance of macrophages, and the same progenitors give rise to either osteoclasts or macrophages, we hypothesize that phenotypic transcription factor-mediated transdifferentiation of macrophages into osteoclasts in situ might be an alternative to increasing the number of osteoclasts. In our previous study, we have confirmed that inactivation of C/EBPα and sustained expression of MITF-E (CM) triggered the phenotypic switch between macrophages and osteoclasts. Based on the above, the aim of the present study is to examine the mechanism underlying initiation and maintenance of CM-mediated transdifferentiation. In addition, in vitro and in vivo models will be transduced with an adenovirus vector encoding a construct overexpressing MITF-E and C/EBPα siRNA under the control of a macrophage-specific promoter, and the function of transdifferented osteoclast will be monitored. In conclusion, we will elucidate the mechanisms underlying CM-mediated transdifferentiation and examine the effects of osteoclasts transdifferentiation on pericardial calcification regression.