The Affiliated Stomatology Hospital, Zhejiang University, School of Medicine, Yan'an Road, Hangzhou, China; Key Laboratory of Oral Biomedical Research of Zhejiang Province, Zhejiang University School of Stomatology, Yan'an Road, Hangzhou, China.
The Affiliated Stomatology Hospital, Zhejiang University, School of Medicine, Yan'an Road, Hangzhou, China; Key Laboratory of Oral Biomedical Research of Zhejiang Province, Zhejiang University School of Stomatology, Yan'an Road, Hangzhou, China.
Differentiation. 2020 Jul-Aug;114:13-19. doi: 10.1016/j.diff.2020.05.002. Epub 2020 May 16.
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-α1, αV, α6, and β1. LN-332 stimulates osteogenic differentiation of MSCs and bone-marrow-derived MSCs (BMSCs) by α3β1/α3β3 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-α2/β1 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-α6β1/αVβ1 and the PI3k/Akt pathways. In addition, a variety of laminin fragments such as iMatrix-411; iMatrix-511; bioactive peptide sequences of LN-α2, 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.
细胞外基质 (ECM) 在不同的发育阶段和多个系统中都起着至关重要的作用。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，其内在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的详细机制的进一步研究。层粘连蛋白 (LN) 是一种合成的重组基底膜蛋白，它可以解决上述问题，因为它是 ECM 的关键组成部分，可以完全且可重复地进行化学定义。本文总结了 LN 在成骨分化和干细胞维持中的功能和机制。LN-111 通过细胞外基质受体整合素-α1、αV、α6 和β1 增强间充质干细胞 (MSCs) 和骨髓祖细胞 (BMPCs) 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) 信号通路刺激 MSCs 和骨髓来源的间充质干细胞 (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 信号通路调节牙周膜细胞 (DFCs) 的成骨分化。LN-511 和 LN-521 通过整合素-α6β1/αVβ1 和 PI3k/Akt 途径维持多能干细胞 (PSCs) 和人胚胎干细胞 (hESCs) 的多能性。此外，多种层粘连蛋白片段，如 iMatrix-411；iMatrix-511；LN-α2 的生物活性肽序列 PPFEGCIWN 和 DLTIDDSYWYRI；以及 LN-332 大球状 3 (LG3)，已被证实可诱导成骨分化。LN511-E8、LN332-E8 片段和层粘连蛋白模拟序列 YIGSR 维持干细胞特性。LN 可能在表面基因标志物、无动物培养和增强成骨因子表达方面具有潜在应用。
