Proinflammatory Mediators Enhance the Osteogenesis of Human Mesenchymal Stem Cells after Lineage Commitment.
Proinflammatory Mediators Enhance the Osteogenesis of Human Mesenchymal Stem Cells after Lineage Commitment.
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DOI：
10.1371/journal.pone.0132781
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Alblas J
中科院分区：
文献类型：
--
作者：
Croes M;Oner FC;Kruyt MC;Blokhuis TJ;Bastian O;Dhert WJ;Alblas J
几种炎症过程是过度骨形成的基础，包括脊柱慢性炎症、急性感染或创伤后关节周围骨化。这表明这些条件下的局部因素具有成骨特性。间充质干细胞（MSCs）及其分化后代通过合成细胞外基质和诱导矿化而促进骨愈合。由于体外实验设计的差异，促炎因子对MSC的成骨潜力存在争议。我们的目标是确定允许不同炎症刺激物的促成骨作用的特定条件。将人骨髓间充质干细胞暴露于肿瘤坏死因子α（TNF-α）和脂多糖（LPS）。细胞在生长培养基或成骨分化培养基中培养。或者，骨形态发生蛋白2（BMP-2）被用作成骨补充剂，以模拟体内条件。碱性磷酸酶活性和钙沉积是成骨的指标。为了阐明谱系定向依赖性效应，MSC在处理前预分化。我们的研究结果表明，TNF-α和LPS不影响MSC的成骨标记物的表达，在没有成骨补充。然而，在成骨分化培养基中或与BMP-2一起，这些介质高度刺激其碱性磷酸酶活性和随后的基质矿化。在前成骨细胞，基质矿化显着增加这些介质，但无论培养条件。我们的研究表明，炎症因子有力地增强了骨髓间充质干细胞的成骨能力。这些特性可以用于骨再生策略。重要的是，MSC向成骨谱系的承诺极大地增强了它们对炎症信号的响应。
Several inflammatory processes underlie excessive bone formation, including chronic inflammation of the spine, acute infections, or periarticular ossifications after trauma. This suggests that local factors in these conditions have osteogenic properties. Mesenchymal stem cells (MSCs) and their differentiated progeny contribute to bone healing by synthesizing extracellular matrix and inducing mineralization. Due to the variation in experimental designs used in vitro, there is controversy about the osteogenic potential of proinflammatory factors on MSCs. Our goal was to determine the specific conditions allowing the pro-osteogenic effects of distinct inflammatory stimuli. Human bone marrow MSCs were exposed to tumor necrosis factor alpha (TNF-α) and lipopolysaccharide (LPS). Cells were cultured in growth medium or osteogenic differentiation medium. Alternatively, bone morphogenetic protein 2 (BMP-2) was used as osteogenic supplement to simulate the conditions in vivo. Alkaline phosphatase activity and calcium deposition were indicators of osteogenicity. To elucidate lineage commitment-dependent effects, MSCs were pre-differentiated prior treatment. Our results show that TNF-α and LPS do not affect the expression of osteogenic markers by MSCs in the absence of an osteogenic supplement. In osteogenic differentiation medium or together with BMP-2 however, these mediators highly stimulated their alkaline phosphatase activity and subsequent matrix mineralization. In pre-osteoblasts, matrix mineralization was significantly increased by these mediators, but irrespective of the culture conditions. Our study shows that inflammatory factors potently enhance the osteogenic capacity of MSCs. These properties may be harnessed in bone regenerative strategies. Importantly, the commitment of MSCs to the osteogenic lineage greatly enhances their responsiveness to inflammatory signals.