Stimulation of Chondrogenic Differentiation of Adult Human Bone Marrow-Derived Stromal Cells by a Moderate-Strength Static Magnetic Field

Stimulation of Chondrogenic Differentiation of Adult Human Bone Marrow-Derived Stromal Cells by a Moderate-Strength Static Magnetic Field
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DOI:
10.1089/ten.tea.2013.0307
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发表时间:
2014-06-01
影响因子:
4.1
通讯作者:
Ethier, C. Ross
Ethier, C. Ross
中科院分区:
医学3区
文献类型:
--
作者:
Amin, Harsh D.;Brady, Mariea Alice;Ethier, C. Ross

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骨关节炎治疗的组织工程策略将受益于在前体细胞中诱导软骨形成的能力。一种这样的细胞来源是骨髓来源的基质细胞(BMSC)。在这里,我们研究了中等强度的静磁场(SMFs)对体外培养的人骨髓基质干细胞软骨分化的影响。将细胞以沉淀形式培养,并暴露于几种强度的SMF持续不同的持续时间。通过逆转录-聚合酶链反应测定早期软骨形成转录因子SOX 9和晚期标记基因ACAN和COL 2A 1的mRNA转录水平,并通过生物化学和组织学方法测定软骨特异性大分子sGAG、胶原蛋白2型(Col 2)和蛋白聚糖的产生。还检查了转化生长因子(TGF)-β信号通路的作用。结果表明,施加0.4T磁场14天,在培养的BMSC中引起强烈的软骨分化反应,只要还存在TGF-β 3,即观察到SMF和TGF-β 3对BMSC软骨分化的协同反应。此外,SMF单独引起培养物中的TGF-β分泌,并且SMF的作用可以被TGF-β受体阻断剂SB-431542消除。这些数据表明,中等强度的磁场可以通过TGF-β依赖性途径诱导BMSCs的软骨形成。这一发现在软骨组织工程策略中具有潜在的重要应用。
Tissue-engineering strategies for the treatment of osteoarthritis would benefit from the ability to induce chondrogenesis in precursor cells. One such cell source is bone marrow-derived stromal cells (BMSCs). Here, we examined the effects of moderate-strength static magnetic fields (SMFs) on chondrogenic differentiation in human BMSCs in vitro. Cells were cultured in pellet form and exposed to several strengths of SMFs for various durations. mRNA transcript levels of the early chondrogenic transcription factor SOX9 and the late marker genes ACAN and COL2A1 were determined by reverse transcription-polymerase chain reaction, and production of the cartilage-specific macromolecules sGAG, collage type 2 (Col2), and proteoglycans was determined both biochemically and histologically. The role of the transforming growth factor (TGF)-beta signaling pathway was also examined. Results showed that a 0.4 T magnetic field applied for 14 days elicited a strong chondrogenic differentiation response in cultured BMSCs, so long as TGF-beta 3 was also present, that is, a synergistic response of a SMF and TGF-beta 3 on BMSC chondrogenic differentiation was observed. Further, SMF alone caused TGF-beta secretion in culture, and the effects of SMF could be abrogated by the TGF-beta receptor blocker SB-431542. These data show that moderate-strength magnetic fields can induce chondrogenesis in BMSCs through a TGF-beta-dependent pathway. This finding has potentially important applications in cartilage tissue-engineering strategies.