BMP12 and BMP13 gene transfer induce ligamentogenic differentiation in mesenchymal progenitor and anterior cruciate ligament cells.

BMP12 and BMP13 gene transfer induce ligamentogenic differentiation in mesenchymal progenitor and anterior cruciate ligament cells.
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DOI:
10.3109/14653241003709652
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发表时间:
2010-07
期刊:
影响因子:
4.5
通讯作者:
Steinert AF
Steinert AF
中科院分区:
医学3区
文献类型:
--
作者:
Haddad-Weber M;Prager P;Kunz M;Seefried L;Jakob F;Murray MM;Evans CH;Nöth U;Steinert AF

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迄今为止,只有很少的数据可用于韧带间充质基质/祖细胞(MSC)和前交叉韧带(ACL)成纤维细胞的分化能力。我们描述了在体外潜力的MSC和ACL细胞进行韧带分化后,与腺病毒载体转导编码人骨形态发生蛋白(BMP)12和BMP 13,也被称为生长和分化因子(GDF)6和7,分别。通过蛋白质印迹分析证实转基因表达至少14天。在I型胶原蛋白水凝胶内细胞培养21天后,两种细胞类型的遗传修饰构建体的组织化学(苏木精/伊红(H&E),Azan和货车Gieson)、免疫组织化学和聚合酶链反应(PCR)分析显示嵌入富含胶原蛋白、波形蛋白、纤连蛋白、核心蛋白聚糖、弹性蛋白、硬化蛋白、腱生蛋白和腱调节蛋白的韧带样基质中的伸长的、有活力的成纤维细胞样细胞。看来MSC和ACL成纤维细胞都能够与这些因子一起进行韧带分化。这些信息可能有助于开发生物学方法来修复和恢复ACL损伤后。
To date there are only very few data available on the ligamentogenic differentiation capacity of mesenchymal stromal/progenitor cells (MSC) and anterior cruciate ligament (ACL) fibroblasts. We describe the in vitro potential of MSC and ACL cells to undergo ligamentogenic differentiation upon transduction with adenoviral vectors encoding the human cDNA for bone morphogenetic protein (BMP) 12 and BMP13, also known as growth and differentiation factors (GDF) 6 and 7, respectively. Transgene expression for at least 14 days was confirmed by Western blot analyzes. After 21 days of cell culture within collagen type I hydrogels, histochemical (hematoxylin/eosin (H&E), Azan and van Gieson), immunohistochemical and polymerase chain reaction (PCR) analyzes of the genetically modified constructs of both cell types revealed elongated, viable fibroblast-like cells embedded in a ligament-like matrix rich in collagens, vimentin, fibronectin, decorin, elastin, scleraxis, tenascin, and tenomodulin. It appears that both MSC and ACL fibroblasts are capable of ligamentogenic differentiation with these factors. This information may aid in the development of biologic approaches to repair and restore ACL after injury.
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