Mansurabadi Raziyeh, Abroun Saeid, Hajifathali Abass, Asri Amir, Atashi Amir, Haghighi Mansoureh
Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Bone Marrow Transplantation Center, Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Cell J. 2017 Spring;19(Suppl 1):27-36. doi: 10.22074/cellj.2017.4480. Epub 2017 May 17.
Multiple Myeloma (MM) is a heterogeneous cytogenetic disorder in which clonal plasma cells proliferate in the bone marrow (BM) and cause bone destruction. The BM microenvironment plays a crucial role in pathogenesis of this disease, and mesenchymal stem cells (MSCs) are one of the key players. Herein, we propose to investigate the expressions of , runt-related transcription factor 2 (), peroxisome proliferator-activated receptor gamma (), and B-cell lymphoma 2 () as factors involved in osteogenesis, adipogenesis, and MSC survival in BM-MSCs from MM patients and normal individuals.
In this experimental study, we isolated MSCs from BM aspirates of MM patients and healthy donors. Total RNA were extracted before and after co-culture with L363 myeloma cells. Gene expressions of , , , and were assessed by quantitive real time polymerase chain reaction (qRT-PCR).
Higher levels of , , and expressions existed in MM- MSCs compared to normally derived (ND)-MSCs. expression decreased in MM- MSCs. We observed different results in the co-culture model.
In general, the MM-MSCs gene expression profile differed compared to ND- MSCs. Upregulation of , , and in MM-MSCs compared to ND- MSCs would result in formation of bone defects. Downregulation of would lead to MM-MSC cell death.
多发性骨髓瘤(MM)是一种异质性细胞遗传学疾病,其中克隆性浆细胞在骨髓(BM)中增殖并导致骨质破坏。骨髓微环境在该疾病的发病机制中起关键作用,间充质干细胞(MSCs)是关键参与者之一。在此,我们提议研究 runt 相关转录因子 2(Runx2)、过氧化物酶体增殖物激活受体γ(PPARγ)和 B 细胞淋巴瘤 2(Bcl-2)作为参与 MM 患者和正常个体骨髓间充质干细胞(BM-MSCs)成骨、脂肪生成和 MSC 存活的因子的表达情况。
在本实验研究中,我们从 MM 患者和健康供体的骨髓抽吸物中分离出 MSCs。在与 L363 骨髓瘤细胞共培养前后提取总 RNA。通过定量实时聚合酶链反应(qRT-PCR)评估 Runx2、PPARγ、Bcl-2 和 Bcl-xL 的基因表达。
与正常来源(ND)的 MSCs 相比,MM-MSCs 中 Runx2、PPARγ 和 Bcl-2 的表达水平更高。Bcl-xL 在 MM-MSCs 中的表达降低。我们在共培养模型中观察到了不同的结果。
总体而言,与 ND-MSCs 相比,MM-MSCs 的基因表达谱有所不同。与 ND-MSCs 相比,MM-MSCs 中 Runx2、PPARγ 和 Bcl-2 的上调会导致骨缺损的形成。Bcl-xL 的下调会导致 MM-MSC 细胞死亡。