Circulating Mesenchymal Stem Cells With Abnormal Osteogenic Differentiation in Patients With Osteoporosis
Circulating Mesenchymal Stem Cells With Abnormal Osteogenic Differentiation in Patients With Osteoporosis
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DOI：
10.1002/art.24884
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发表时间：
2009-11-01
影响因子：
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通讯作者：
Lo Cascio, Vincenzo
中科院分区：
文献类型：
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作者：
Carbonare, Luca Dalle;Valenti, Maria Teresa;Lo Cascio, Vincenzo
目标。虽然破骨细胞在骨丢失中的作用已经得到了很好的研究，但成骨细胞系细胞的参与还没有完全阐明。一些基因有助于从间充质干细胞(MSCs)向正常的成骨细胞分化，但对它们在骨质疏松发病机制中的作用仍缺乏了解。本研究旨在评估成骨基因表达的变化可能是导致骨丢失的一个机制。我们研究了31例骨质疏松症患者和20例正常献血者外周血中骨髓间充质干细胞的成骨分化过程。诱导分化3、8、15d后，采用集落形成单位-成纤维细胞实验进行鉴定，并在成骨细胞培养液中培养，分析转录因子RUNT相关转录因子2(RUNX-2)和SP7以及骨相关基因COL1A1、SPARC和SPP1。此外，为了确定两组之间在破骨细胞和成骨细胞激活方面的可能差异，我们对成骨细胞培养上清液中的骨保护素(OPG)和RANKL水平进行了定量。与正常供者相比，骨质疏松患者外周血中的MSCs明显增多。相反，基因表达分析显示骨质疏松症患者RUNX2、SP7、COL1A1、SPARC和SPP1表达下调，并与较低的OPG：RANKL比率有关。这些结果提示，成骨细胞分化的改变可能参与了骨质疏松的发病机制。本研究中使用的非侵入性方法可作为研究间质参与骨疾病的有用工具。
Objective. While the role of osteoclasts in bone loss has been well investigated, the involvement of osteoblast-lineage cells has not been completely elucidated. Several genes contribute to normal osteoblastic differentiation from mesenchymal stem cells (MSCs), but an understanding of their role in the pathogenesis of osteoporosis is still lacking. The present study was undertaken to evaluate a possible alteration of osteogenic gene expression as a mechanism contributing to bone loss.Methods. We studied the osteogenic differentiation process in MSCs obtained from the peripheral blood of 31 patients with osteoporosis and 20 normal donors. The cells were evaluated by colony-forming unit-fibroblastic assay and cultured in osteogenic medium to analyze the transcription factors runt-related transcription factor 2 (RUNX-2) and Sp7 and the bone-related genes COL1A1, SPARC, and SPP1 after 3, 8, and 15 days of differentiation. In addition, to determine possible differences between the 2 groups in terms of osteoclastic and osteoblastic activation, we quantified the osteoprotegerin (OPG) and RANKL levels in the supernatants of osteoblastic culture.Results. Circulating MSCs were increased in osteoporosis patients compared with normal donors. In contrast, gene expression analysis revealed down-regulation of RUNX2, Sp7, COL1A1, SPARC, and SPP1 in patients with osteoporosis, associated with a lower OPG:RANKL ratio.Conclusion. These results suggest that an alteration of osteoblastic differentiation may contribute to the pathogenesis of osteoporosis. The noninvasive approach used in the present study could be proposed as a useful tool for studying mesenchymal involvement in bone diseases.