Unité de Thérapie Cellulaire, Assistance Publique-Hôpitaux de Paris, Hôpital Saint Louis, Paris, France.
Stem Cells Dev. 2012 Jan 20;21(2):239-48. doi: 10.1089/scd.2011.0365. Epub 2011 Oct 18.
Gaucher disease (GD) is a lysosomal storage disorder due to glucocerebrosidase (GBA) deficiency. Mechanisms leading to the emergence of hematological and skeletal manifestations observed in GD are poorly explained. Bone marrow (BM) mesenchymal stem cells (MSCs) are multipotent progenitors that participate in the regulation of bone mass. MSCs should thus represent a cell population involved in the development or progression of bone disease in GD. In a chemical model of GD obtained with Conduritol β epoxide (CBE), a specific inhibitor of GBA activity, we functionally characterized BM MSCs and specifically analyzed their capacity to differentiate into osteoblasts. GBA deficiency obtained with CBE treatment, leads to a dramatic impairment of MSCs proliferation and to morphological abnormalities. Although the capacity of MSCs to differentiate into osteoblasts was not modified, the levels of several soluble factors that regulate bone metabolism were increased in MSCs treated with CBE, compared with untreated MSCs. Moreover, addition of conditioned media from CBE-treated MSCs on monocyte-derived osteoclasts cultured on bone matrix leads to an increase of resorption areas. These data suggested that, in GD, MSCs represents a stem cell population that is likely to be involved in bone pathogenesis.
戈谢病（GD）是一种由于葡萄糖脑苷脂酶（GBA）缺乏引起的溶酶体贮积症。导致 GD 中观察到的血液学和骨骼表现出现的机制尚未得到很好的解释。骨髓（BM）间充质干细胞（MSCs）是多能祖细胞，参与调节骨量。因此，MSCs 应该代表参与 GD 中骨骼疾病发展或进展的细胞群体。在使用特异性 GBA 活性抑制剂 Conduritol β epoxide（CBE）获得的 GD 化学模型中，我们对 BM MSCs 进行了功能表征，并特别分析了它们分化为成骨细胞的能力。用 CBE 处理获得的 GBA 缺乏会导致 MSCs 增殖的严重受损和形态异常。尽管 CBE 处理的 MSCs 分化为成骨细胞的能力没有改变，但与未处理的 MSCs 相比，调节骨代谢的几种可溶性因子的水平在 CBE 处理的 MSCs 中增加。此外，将来自 CBE 处理的 MSCs 的条件培养基添加到在骨基质上培养的单核细胞来源的破骨细胞上，导致吸收面积增加。这些数据表明，在 GD 中，MSCs 代表一种可能参与骨发病机制的干细胞群体。
