Enhanced osteogenesis of adipose derived stem cells with Noggin suppression and delivery of BMP-2.
Enhanced osteogenesis of adipose derived stem cells with Noggin suppression and delivery of BMP-2.
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DOI：
10.1371/journal.pone.0072474
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Lee M
中科院分区：
文献类型：
--
作者：
Fan J;Park H;Tan S;Lee M
骨形态发生蛋白（BMP）被认为是最有效的骨诱导因子。然而，BMP是高度多效性的分子，其超生理的高剂量需求导致不良副作用和低效的骨形成。因此，需要开发能够有效补充BMP活性的替代骨诱导生长因子策略。在这项研究中，我们内在地刺激BMP信号在脂肪来源的干细胞（ASCs）下调头蛋白，一种有效的BMP拮抗剂，使用RNAi策略。用noggin shRNA转导的ASCs显著增强了细胞的成骨分化。随后通过用显著降低剂量的外源性BMP刺激ASC来增强内源性BMP的效力。当用BMP-2处理时，头蛋白shRNA处理的ASC中的矿化水平与用10倍多的BMP-2处理的对照shRNA处理的细胞的矿化水平相当。头蛋白抑制+ BMP-2以增强骨生成的互补策略在3D体外环境中使用由壳聚糖（CH）、硫酸软骨素（CS）和其表面上的磷灰石层组成的支架被进一步证实，所述支架被设计成缓慢释放BMP-2。这一发现支持了这种互补策略在骨再生中的新治疗潜力。
Bone morphogenetic proteins (BMPs) are believed to be the most potent osteoinductive factors. However, BMPs are highly pleiotropic molecules and their supra-physiological high dose requirement leads to adverse side effects and inefficient bone formation. Thus, there is a need to develop alternative osteoinductive growth factor strategies that can effectively complement BMP activity. In this study, we intrinsically stimulated BMP signaling in adipose derived stem cells (ASCs) by downregulating noggin, a potent BMP antagonist, using an RNAi strategy. ASCs transduced with noggin shRNA significantly enhanced osteogenic differentiation of cells. The potency of endogenous BMPs was subsequently enhanced by stimulating ASCs with exogenous BMPs at a significantly reduced dose. The level of mineralization in noggin shRNA treated ASCs when treated with BMP-2 was comparable to that of control shRNA treated cell treated with 10-fold more BMP-2. The complementary strategy of noggin suppression + BMP-2 to enhance osteogenesis was further confirmed in 3D in vitro environments using scaffolds consisting of chitosan (CH), chondroitin sulfate (CS), and apatite layer on their surfaces designed to slowly release BMP-2. This finding supports the novel therapeutic potential of this complementary strategy in bone regeneration.
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影响因子：
4
作者：
James, Aaron W.;Levi, Benjamin;Longaker, Michael T.
通讯作者：
Longaker, Michael T.
脂肪衍生的干细胞的分离及其诱导对软骨表型的诱导。
影响因子：
14.8
作者：
通讯作者：
--
DOI：
10.1016/j.spinee.2005.02.014
发表时间：
2005-11-01
期刊：
The spine journal : official journal of the North American Spine Society
影响因子：
--
作者：
Carlisle, Elliot;Fischgrund, Jeffrey S
通讯作者：
Fischgrund, Jeffrey S
影响因子：
6.2
作者：
Kilgore, Meredith L.;Morrisey, Michael A.;Delzell, Elizabeth
通讯作者：
Delzell, Elizabeth
影响因子：
56.9
作者：
LANGER, R;VACANTI, JP
通讯作者：
VACANTI, JP