骨形态发生蛋白-2在肝包虫外囊壁钙化中的作用

Effect of bone morphogenetic protein BMP-2 on the calcification of hydatid cysts

为探讨骨形态发生蛋白-2(BMP-2)在囊型包虫外囊壁钙化中所起的作用。采用分离肝包虫囊肿囊壁细胞并诱导其向成骨分化的方法,同时成骨培养基中添加不同浓度的重组人源BMP-2(rh BMP-2)和抑制剂并诱导细胞成骨分化,茜素红染色评估囊壁细胞成骨分化能力;通过观察囊肿情况和对囊壁组织行免疫组化,评估BMP-2因子对囊壁钙化的影响。结果显示,成骨诱导后,囊壁细胞矿化结节增多,外源性的rh BMP-2可促进囊壁细胞矿化,而抑制剂却抑制了这种效果。在肝包虫的动物模型中,抑制剂抑制囊壁细胞的钙化,使得囊肿变小、虫体活力减低。由此可知,包虫囊肿囊壁细胞具有成骨分化潜能,体外成骨诱导可获得成骨细胞样表型;BMP-2促进包虫囊肿囊壁细胞钙化;药理学调控作用下的囊壁钙化将成为包虫病新的治疗靶点。

Objective to evaluate the effect of modulating BMP-2 signaling on the calcification of hydatid pericyst. Methods Pericyst cells were isolated from hepatic hydatid cysts. These cells were cultured with osteogenic media and were evaluated for mineralization capacity using Alizarin Red staining. Cells were also treated with different doses of recombinant human BMP-2 and BMP-2 inhibitor, and the mineralization capacity were analyzed using Alizarin Red staining. The effects of inhibiting BMP-2 signaling on calcification of pericyst walls were evaluated through insight into hydatid cysts themselves and immunohistochemical analysis. Results Cells within the pericyst showed high levels of mineralized nodule formation, as induced by osteogenic media. These effect could be intensified by adding recombinant human BMP-2（rh BMP-2） and inhibited by BMP-2 inhibitor. In the animal model of cystic echinococcosis, inhibition of BMP-2 signaling decreased calcification of the pericyst wall, which was associated with decreased cysts and lower viability of protoscoleces.Conclusion Cells within the pericysts acquire an osteoblast-like phenotype and have osteogenic potential. BMP-2 increases hydatid cyst calcification. Pharmacological mediation of calcification in pericysts may lead to new strategies for therapeutic intervention of hydatid disease.