Dipartimento di Scienze Mediche, Università di Milano e U.O. Ematologia 1, Fondazione IRCCS Policlinico, Milan, Italy.
Exp Hematol. 2010 Feb;38(2):141-53. doi: 10.1016/j.exphem.2009.11.009. Epub 2009 Dec 4.
Multiple myeloma (MM) is characterized by a high incidence of osteolytic bone lesions, which have been previously correlated with the gene expression profiles of MM cells. The aim of this study was to investigate the transcriptional patterns of cells in the bone microenvironment and their relationships with the presence of osteolysis in MM patients.
Both mesenchymal (MSC) and osteoblastic (OB) cells were isolated directly from bone biopsies of MM patients and controls to perform gene expression profiling by microarrays and real-time polymerase chain reaction on selected bone-related genes.
We identified a series of upregulated and downregulated genes that were differentially expressed in the MSC cells of osteolytic and nonosteolytic patients. Comparison of the osteolytic and nonosteolytic samples also showed that the MSC cells and OB had distinct transcriptional patterns. No significantly modulated genes were found in the OBs of the osteolytic and nonosteolytic patients.
Our data suggest that the gene expression profiles of cells of the bone microenvironment are different in MM patients and controls, and that MSC cells, but not OBs, have a distinct transcriptional pattern associated with the occurrence of bone lesions in MM patients. These data support the idea that alterations in MSC cells may be involved in MM bone disease.
多发性骨髓瘤(MM)的特征是溶骨性骨病变发生率高,此前已将其与 MM 细胞的基因表达谱相关联。本研究旨在研究骨微环境中细胞的转录模式及其与 MM 患者溶骨性的关系。
直接从 MM 患者和对照者的骨活检中分离间充质(MSC)和成骨细胞(OB),通过微阵列和实时聚合酶链反应对选定的与骨相关的基因进行基因表达谱分析。
我们确定了一系列在溶骨性和非溶骨性患者的 MSC 细胞中差异表达的上调和下调基因。对溶骨性和非溶骨性样本的比较还表明,MSC 细胞和 OB 具有不同的转录模式。在溶骨性和非溶骨性患者的 OB 中未发现明显调节的基因。
我们的数据表明,骨微环境中细胞的基因表达谱在 MM 患者和对照者中存在差异,并且 MSC 细胞而非 OB 具有与 MM 患者骨病变发生相关的独特转录模式。这些数据支持 MSC 细胞的改变可能与 MM 骨病有关的观点。