GDFs promote tenogenic characteristics on human periodontal ligament-derived cells in culture at late passages
GDFs promote tenogenic characteristics on human periodontal ligament-derived cells in culture at late passages
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DOI：
10.3109/08977194.2013.830611
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发表时间：
2013-10
期刊：
影响因子：
1.8
通讯作者：
Dengsheng Xia;Y. Sumita;Younan Liu;Y. Tai;Jinsong Wang;M. Uehara;Hideki Agata;H. Kagami;Z. Fan
中科院分区：
文献类型：
--
作者：
Dengsheng Xia;Y. Sumita;Younan Liu;Y. Tai;Jinsong Wang;M. Uehara;Hideki Agata;H. Kagami;Z. Fan
摘要肌腱/韧带损伤是世界范围内的主要残疾。牙周韧带(PDL)连接牙齿和骨骼，类似于肌腱/韧带到骨骼的植入。PDL来源的细胞既表达骨/骨形成基因，又表达Teno/韧带生成基因。然而，一种有效的诱导PDLCs发生分化的方法还没有得到彻底的研究。因此，本研究检测了生长分化因子(GDFs)是否能增强人PDLCs的肌腱形成特性，作为肌腱/韧带工程的潜在细胞来源。结果表明，重组GDF-5/GDF-7抑制第3~6代PDLCs的碱性磷酸酶(ALP)活性，而GDF-5增强牙髓来源细胞和间充质干细胞的ALP活性。GDF-5(尤其是在10 ng/ml浓度时)诱导P4-6 PDLCs早期(硬化轴)和成熟(肌腱调节蛋白、聚集素、胶原蛋白3)致腱基因的高表达，同时抑制成骨、成软骨和成脂分化的特定转录因子的表达。外源性GDF可能导致PDLCs在几代培养过程中扩增，成为肌腱/韧带工程有用的细胞来源。
Abstract Tendon/ligament injures are leading disabilities worldwide. The periodontal ligament (PDL) connects teeth to bone, and is comparable to a tendon/ligament-to-bone insertion. PDL-derived cells (PDLCs) express both osteo/cementogenesis and teno/ligamentogenesis genes. However, an efficient method to induce a tenogenic differentiation of PDLCs has not been thoroughly examined. Therefore, this study tested if growth/differentiation factors (GDFs) enhanced tenogenic characteristics of human PDLCs, as a potential cell source for tendon/ligament engineering. Results demonstrated recombinant GDF-5/GDF-7 inhibited alkaline phosphatase (ALP) activity of PDLCs from passage 3 to 6, while GDF-5 enhanced ALP in dental pulp-derived cells and mesenchymal stem cells. GDF-5 (particularly at 10 ng/ml concentration) induced high expression of both early (scleraxis) and mature (tenomodulin, aggrecan, collagen3) tenogenic genes in P4-6 PDLCs, while inhibiting expression of specific transcription-factors for osteogenic, chondrogenic and adipogenic differentiation. Exogenous GDFs might lead PDLCs being expanded in culture during several passages to highly useful cell source for tendon/ligament engineering.