Differential effects of dexamethasone on the chondrogenesis of mesenchymal stromal cells: influence of microenvironment, tissue origin and growth factor.
Differential effects of dexamethasone on the chondrogenesis of mesenchymal stromal cells: influence of microenvironment, tissue origin and growth factor.
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DOI：
10.22203/ecm.v022a23
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发表时间：
2011-11
影响因子：
3.1
通讯作者：
N. Shintani;E. B. Hunziker
中科院分区：
文献类型：
--
作者：
N. Shintani;E. B. Hunziker
间充质基质细胞（MSC），其存在于各种组织中，用于软骨组织的工程化。地塞米松（DEX）--一种合成糖皮质激素--几乎总是用于增强生长因子诱导的MSC体外软骨形成，尽管这种作用仅在转化生长因子-β（TGF-β）刺激的骨髓源性MSC中得到实验证明。临床上，全身性糖皮质激素治疗与不良副作用（例如，骨质流失和感染易感性增加）。因此，应避免或限制使用这些药剂。我们假设DEX对MSC的软骨形成的影响取决于其组织来源和微环境[细胞外基质（ECM）的存在或不存在]，以及生长因子的性质。我们研究了其对TGF-β1和骨形态发生蛋白2（BMP-2）诱导的MSC软骨形成的影响，作为组织来源（骨髓与滑膜）和微环境[细胞聚集体（无ECM）与外植体（存在天然ECM）]的函数。在骨髓来源的MSC聚集体中，DEX通过上调软骨基因增强TGF-β1诱导的软骨形成，但对BMP-2诱导的反应影响不大。在滑膜间充质干细胞聚集体中，DEX对TGF-β1或BMP-2诱导的软骨形成没有显著影响。在滑膜外植体中，DEX几乎完全抑制BMP-2诱导的软骨形成，但对TGF-β1诱导的反应几乎没有影响。我们的数据表明，类固醇不是不可缺少的骨髓间充质干细胞在体外的软骨形成。它们的影响取决于环境（MSC的组织来源，它们的微环境和生长因子的性质）。这一发现对基于MSC的软骨修复方法具有重要意义。
Mesenchymal stromal cells (MSCs), which reside within various tissues, are utilized in the engineering of cartilage tissue. Dexamethasone (DEX)--a synthetic glucocorticoid--is almost invariably applied to potentiate the growth-factor-induced chondrogenesis of MSCs in vitro, albeit that this effect has been experimentally demonstrated only for transforming-growth-factor-beta (TGF-β)-stimulated bone-marrow-derived MSCs. Clinically, systemic glucocorticoid therapy is associated with untoward side effects (e.g., bone loss and increased susceptibility to infection). Hence, the use of these agents should be avoided or limited. We hypothesize that the influence of DEX on the chondrogenesis of MSCs depends upon their tissue origin and microenvironment [absence or presence of an extracellular matrix (ECM)], as well as upon the nature of the growth factor. We investigated its effects upon the TGF-β1- and bone-morphogenetic-protein 2 (BMP-2)-induced chondrogenesis of MSCs as a function of tissue source (bone marrow vs. synovium) and microenvironment [cell aggregates (no ECM) vs. explants (presence of a natural ECM)]. In aggregates of bone-marrow-derived MSCs, DEX enhanced TGF-β1-induced chondrogenesis by an up-regulation of cartilaginous genes, but had little influence on the BMP-2-induced response. In aggregates of synovial MSCs, DEX exerted no remarkable effect on either TGF-β1- or BMP-2-induced chondrogenesis. In synovial explants, DEX inhibited BMP-2-induced chondrogenesis almost completely, but had little impact on the TGF-β1-induced response. Our data reveal that steroids are not indispensable for the chondrogenesis of MSCs in vitro. Their influence is context dependent (tissue source of the MSCs, their microenvironment and the nature of the growth-factor). This finding has important implications for MSC based approaches to cartilage repair.