Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan.
J Biomed Mater Res A. 2010 Sep 1;94(3):673-82. doi: 10.1002/jbm.a.32693.
Biomaterials not only serve as scaffolds for bone regeneration, but may also exhibit inductive capability for bone growth. The goal of this study was to identify the best extracellular matrix protein for enhancing osteogenesis by hMSCs (human mesenchymal stem cells) and to investigate the underlying mechanism. Coating with collagen I, but not fibronectin, laminin, gelatin, and poly-L-lysine, enhanced late cell proliferation and promoted osteogenesis by hMSCs, as evidenced by an increase in Alizarin Red S staining, alkaline phosphatase activity and mRNA levels of Runx2 and osteocalcin. Coating with collagen I induced activation of ERK and Akt but not FAK, and treatment with PD98059 and LY294002 blocked the activation of ERK and Akt, respectively. Interestingly, LY294002 also blocked ERK activation, indicating the activation of PI3K/ERK pathway upon contact with collagen I. Furthermore, PD98059 or LY294002 abolished collagen I-induced promotion of osteogenesis by hMSCs. However, blocking antibodies against alpha2beta1 integrins did not inhibit collagen I-induced osteogenesis by hMSCs. These data demonstrate that collagen I promotes proliferation and osteogenesis of hMSCs via activation of ERK and Akt pathways.
生物材料不仅可以作为骨再生的支架，还可能具有诱导骨生长的能力。本研究旨在确定最佳的细胞外基质蛋白，以增强人骨髓间充质干细胞（hMSCs）的成骨作用，并探讨其潜在机制。用胶原蛋白 I 而不是纤连蛋白、层粘连蛋白、明胶和聚-L-赖氨酸包被可增强 hMSCs 的晚期细胞增殖并促进其成骨作用，这表现在茜素红 S 染色、碱性磷酸酶活性以及 Runx2 和骨钙素的 mRNA 水平增加。胶原蛋白 I 包被诱导 ERK 和 Akt 的激活，但不诱导 FAK 的激活，而 PD98059 和 LY294002 处理分别阻断了 ERK 和 Akt 的激活。有趣的是，LY294002 也阻断了 ERK 的激活，表明胶原蛋白 I 接触后激活了 PI3K/ERK 通路。此外，PD98059 或 LY294002 消除了胶原蛋白 I 对 hMSCs 成骨作用的促进。然而，针对α2β1 整合素的阻断抗体并不能抑制胶原蛋白 I 诱导的 hMSCs 成骨作用。这些数据表明，胶原蛋白 I 通过激活 ERK 和 Akt 通路促进 hMSCs 的增殖和成骨作用。
