Laminin-5 induces osteogenic gene expression in human mesenchymal stem cells through an ERK-dependent pathway
Laminin-5 induces osteogenic gene expression in human mesenchymal stem cells through an ERK-dependent pathway
复制标题
DOI：
10.1091/mbc.e04-08-0695
复制
发表时间：
2005-02-01
影响因子：
3.3
通讯作者：
Plopper, GE
中科院分区：
文献类型：
--
作者：
Klees, RF;Salasznyk, RM;Plopper, GE
层粘连蛋白家族对于管理多种细胞活动（包括迁移、粘附和分化）至关重要。在骨骼中，层粘连蛋白在控制人间充质干细胞（hMSC）成骨分化中的作用尚不清楚。我们在此报道，laminin-5 存在于骨骼中并由 hMSC 表达。从骨中分离的 hMSC 合成 laminin-5，并通过 alpha3beta1 整合素粘附到外源 laminin-5。粘附层粘连蛋白-5 可在 30 分钟内激活细胞外信号相关激酶 (ERK)，并在 8 天内导致成骨转录因子 Runx2/CBFA-1 磷酸化。铺在层粘连蛋白-5 上 16 天的细胞表达成骨标记基因水平增加，铺在层粘连蛋白 5 上 21 天的细胞沉积矿化基质，表明成骨分化。添加 ERK 抑制剂 PD98059 可减轻这些影响。我们的结论是，与层粘连蛋白-5 接触足以激活 ERK 并刺激 hMSC 中的成骨分化。
The laminin family of proteins is critical for managing a variety of cellular activities including migration, adhesion, and differentiation. In bone, the roles of laminins in controlling osteogenic differentiation of human mesenchymal stem cells (hMSC) are unknown. We report here that laminin-5 is found in bone and expressed by hMSC. hMSC isolated from bone synthesize laminin-5 and adhere to exogenous laminin-5 through alpha3beta1 integrin. Adhesion to laminin-5 activates extracellular signal-related kinase (ERK) within 30 min and leads to phosphorylation of the osteogenic transcription factor Runx2/CBFA-1 within 8 d. Cells plated on laminin-5 for 16 d express increased levels of osteogenic marker genes, and those plated for 21 d deposit a mineralized matrix, indicative of osteogenic differentiation. Addition of the ERK inhibitor PD98059 mitigates these effects. We conclude that contact with laminin-5 is sufficient to activate ERK and to stimulate osteogenic differentiation in hMSC.