Annexin-enriched osteoblast-derived vesicles act as an extracellular site of mineral nucleation within developing stem cell cultures.
Annexin-enriched osteoblast-derived vesicles act as an extracellular site of mineral nucleation within developing stem cell cultures.
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DOI：
10.1038/s41598-017-13027-6
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发表时间：
2017-10-03
影响因子：
4.6
通讯作者：
Grover LM
中科院分区：
文献类型：
--
作者：
Davies OG;Cox SC;Williams RL;Tsaroucha D;Dorrepaal RM;Lewis MP;Grover LM
细胞外囊泡（EVs）作为促进组织再生的天然递送载体的应用可能代表着医学领域一个令人兴奋的新阶段。我们试图确定矿化成骨细胞（mo - ev）衍生的ev在间充质干细胞（MSC）培养中诱导矿化的能力，并描述其潜在的生化机制。引人注目的是，我们发现在MSC培养中添加mo - ev显著（P < 0.05）增强了碱性磷酸酶的表达，以及矿化率和体积，超过了目前的黄金标准BMP-2。有趣的是，这些影响仅在外源磷酸盐存在的情况下观察到。从非矿化成骨细胞（NMO-EVs）衍生的ev没有发现超出控制的矿化。ev的比较无标签LC-MS/MS分析表明，矿化增强可能归因于桥接胶原（主要与成骨细胞通信相关）和其他非胶原蛋白向发育中的细胞外基质的输送。特别是与ev相关的膜联蛋白钙通道蛋白，它与富含磷脂的膜形成核核，并支持磷灰石前矿物相的形成，这是用红外光谱识别的。这些发现支持了ev作为矿物成核的早期位点的作用，并证明了它们促进硬组织再生的价值。
The application of extracellular vesicles (EVs) as natural delivery vehicles capable of enhancing tissue regeneration could represent an exciting new phase in medicine. We sought to define the capacity of EVs derived from mineralising osteoblasts (MO-EVs) to induce mineralisation in mesenchymal stem cell (MSC) cultures and delineate the underlying biochemical mechanisms involved. Strikingly, we show that the addition of MO-EVs to MSC cultures significantly (P < 0.05) enhanced the expression of alkaline phosphatase, as well as the rate and volume of mineralisation beyond the current gold-standard, BMP-2. Intriguingly, these effects were only observed in the presence of an exogenous phosphate source. EVs derived from non-mineralising osteoblasts (NMO-EVs) were not found to enhance mineralisation beyond the control. Comparative label-free LC-MS/MS profiling of EVs indicated that enhanced mineralisation could be attributed to the delivery of bridging collagens, primarily associated with osteoblast communication, and other non-collagenous proteins to the developing extracellular matrix. In particular, EV-associated annexin calcium channelling proteins, which form a nucleational core with the phospholipid-rich membrane and support the formation of a pre-apatitic mineral phase, which was identified using infrared spectroscopy. These findings support the role of EVs as early sites of mineral nucleation and demonstrate their value for promoting hard tissue regeneration.
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DOI：
10.1073/pnas.1208916109
发表时间：
2012-08-28
影响因子：
11.1
作者：
Boonrungsiman, Suwimon;Gentleman, Eileen;Stevens, Molly M.
通讯作者：
Stevens, Molly M.
DOI：
10.1083/jcb.35.1.81
发表时间：
1967-10
期刊：
The Journal of cell biology
影响因子：
--
作者：
Anderson HC
通讯作者：
Anderson HC
影响因子：
4.4
作者：
Cox, Juergen;Neuhauser, Nadin;Mann, Matthias
通讯作者：
Mann, Matthias
影响因子：
3.4
作者：
Brown, Raquel J.;Mallory, Christopher;McDougal, Owen M.;Oxford, Julia Thom
通讯作者：
Oxford, Julia Thom
影响因子：
6.2
作者：
Chen, Neal X.;O'Neill, Kalisha D.;Moe, Sharon M.
通讯作者：
Moe, Sharon M.