LISIN, Departamento de Ciencias Biológicas, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, La Plata 1900, Argentina.
Gene. 2013 Dec 15;532(2):186-91. doi: 10.1016/j.gene.2013.09.072. Epub 2013 Sep 26.
Gaucher disease (GD) is caused by mutations in the GBA gene that confer a deficient level of activity of glucocerebrosidase (GCase). This deficiency leads to accumulation of the glycolipid glucocerebroside in the lysosomes of cells of monocyte/macrophage system. Type I GD is the mildest form and is characterized by the absence of neuronopathic affection. Bone compromise in Gaucher disease patients is the most disabling aspect of the disease. However, pathophysiological aspects of skeletal alterations are still poorly understood. The homeostasis of bone tissue is maintained by the balanced processes of bone resorption by osteoclasts and formation by osteoblasts. We decided to test whether bone resorption and/or bone formation could be altered by the use of a chemical in vitro murine model of Gaucher disease. We used two sources of cells from monocyte/macrophages lineage isolated from normal mice, splenocytes (S) and peritoneal macrophages (PM), and were exposed to CBE, the inhibitor of GCase (S-CBE and PM-CBE, respectively). Addition of both conditioned media (CM) from S-CBE and PM-CBE induced the differentiation of osteoclasts precursors from bone marrow to mature and functional osteoclasts. TNF-α could be one of the factors responsible for this effect. On the other hand, addition of CM to an osteoblast cell culture resulted in a reduction in expression of alkaline phosphatase and mineralization process. In conclusion, these results suggest implication of changes in both bone formation and bone resorption and are consistent with the idea that both sides of the homeostatic balance are affected in GD.
戈谢病（GD）是由 GBA 基因突变引起的，该突变导致葡萄糖脑苷脂酶（GCase）的活性降低。这种缺陷导致糖脂葡萄糖脑苷脂在单核/巨噬细胞系统细胞的溶酶体中积累。I 型 GD 是最温和的形式，其特征是没有神经元病变。戈谢病患者的骨骼损伤是该疾病最致残的方面。然而，骨骼改变的病理生理方面仍知之甚少。骨骼组织的内稳定是通过破骨细胞的骨吸收和成骨细胞的形成这两个平衡过程来维持的。我们决定测试使用戈谢病的体外化学小鼠模型是否可以改变骨吸收和/或骨形成。我们使用了两种源自正常小鼠的单核/巨噬细胞谱系的细胞来源，脾细胞（S）和腹腔巨噬细胞（PM），并将其暴露于 GCase 的抑制剂 CBE（分别为 S-CBE 和 PM-CBE）。S-CBE 和 PM-CBE 的两种条件培养基（CM）的添加均诱导了骨髓中破骨细胞前体向成熟和功能成熟的破骨细胞的分化。TNF-α可能是引起这种效应的因素之一。另一方面，CM 添加到成骨细胞培养物中导致碱性磷酸酶的表达和矿化过程减少。总之，这些结果表明骨形成和骨吸收都发生了变化，这与 GD 中平衡的两个方面都受到影响的观点一致。
