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首页> 外文期刊>Differentiation: The Journal of the International Society of Differentiation >Laminins in osteogenic differentiation and pluripotency maintenance
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Laminins in osteogenic differentiation and pluripotency maintenance

机译：骨质发生分化和多能性维护中的层状

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摘要

Extracellular matrix (ECM) plays an integral role in different developmental stages and in multiple systems. However, due to ECM being composed of various extracellular components (growth factors, cytokines, and hormones), its innate complexity and the lack of any efficient purification techniques limit further research into the detailed mechanisms of its role in cellular activities. Laminin (LN), a synthetic recombinant basement membrane protein, can solve the above problems as it is a critical component of ECM and can be completely and reproducibly chemically defined. This article summarizes the functions and mechanisms of LN during osteogenic differentiation and stemness maintenance. LN-111 enhances osteogenic differentiation of mesenchymal stem cells (MSCs) and bone marrow progenitor cells (BMPCs) via the ECM receptor integrin-alpha 1, alpha V, alpha 6, and beta 1. LN-332 stimulates osteogenic differentiation of MSCs and bone-marrow-derived MSCs (BMSCs) by alpha 3 beta 1/alpha 3 beta 3 integrin-mediated activation of the focal adhesion kinase (FAK)/extracellular-signal-regulated kinase (ERK), Wnt5a, and bone morphogenic proteins (BMP) signaling pathways. Moreover, LN-111, LN-211, and LN-332 regulate the osteogenic differentiation of dental follicle cells (DFCs) via the integrin-alpha 2/beta 1 and FAK/ERK signaling pathways. LN-511 and LN-521 can preserve the pluripotency of pluripotent stem cells (PSCs) and human embryonic stem cells (hESCs) via the integrin-alpha 6 beta 1/alpha V beta 1 and the PI3k/Akt pathways. In addition, a variety of laminin fragments such as iMatrix-411; iMatrix-511; bioactive peptide sequences of LN-alpha 2, PPFEGCIWN, and DLTIDDSYWYRI; and LN-332 large globular 3 (LG3), were confirmed to induce osteogenic differentiation. LN511-E8, LN332-E8 fragments, and the laminin-mimicking sequence YIGSR sustain stemness. LN may have potential applications in surface gene markers, xeno-free cultures, and enhancing the expression of osteogenic factors.
机译：细胞外基质（Extracellular matrix，ECM）在不同发育阶段和多个系统中起着不可或缺的作用。然而，由于ECM由各种细胞外成分（生长因子、细胞因子和激素）组成，其固有的复杂性以及缺乏任何有效的纯化技术限制了对其在细胞活动中作用的详细机制的进一步研究。层粘连蛋白（LN）是一种人工合成的重组基底膜蛋白，可以解决上述问题，因为它是ECM的关键成分，并且可以完全且可重复地进行化学定义。本文综述了LN在成骨分化和保持骨干中的作用和机制。LN-111通过ECM受体整合素α1、αV、α6和β1增强间充质干细胞（MSC）和骨髓祖细胞（BMPC）的成骨分化。LN-332通过α3β1/α3β3整合素介导的粘着斑激酶（FAK）/细胞外信号调节激酶（ERK）、Wnt5a和骨形态发生蛋白（BMP）信号通路的激活，刺激MSC和骨髓源性MSC（BMSCs）的成骨分化。此外，LN-111、LN-211和LN-332通过整合素α2/β1和FAK/ERK信号通路调节牙囊细胞（DFC）的成骨分化。LN-511和LN-521可以通过整合素α6β1/αVβ1和PI3k/Akt途径维持多能干细胞（PSC）和人类胚胎干细胞（HESC）的多能性。此外，多种层粘连蛋白片段，如iMatrix-411；iMatrix-511；LNα2、PPFEGCIWN和DLTIDDSYWYRI的生物活性肽序列；LN-332大球蛋白3（LG3）被证实能诱导成骨分化。LN511-E8、LN332-E8片段和层粘连蛋白模拟序列YIGSR维持干性。LN可能在表面基因标记、无异种培养和增强成骨因子表达方面有潜在的应用。

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