Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, 315 Ferst Drive NW, Atlanta, GA 30332-0363, USA.
Biomaterials. 2010 Apr;31(10):2728-35. doi: 10.1016/j.biomaterials.2009.12.029. Epub 2010 Jan 6.
Microstructured and high surface energy titanium substrates increase osseointegration in vivo. In vitro, osteoblast differentiation is increased, but effects of the surface directly on multipotent mesenchymal stem cells (MSCs) and consequences for MSCs in the peri-implant environment are not known. We evaluated responses of human MSCs to substrate surface properties and examined the underlying mechanisms involved. MSCs exhibited osteoblast characteristics (alkaline phosphatase, RUNX2, and osteocalcin) when grown on microstructured Ti; this effect was more robust with increased hydrophilicity. Factors produced by osteoblasts grown on microstructured Ti were sufficient to induce co-cultured MSC differentiation to osteoblasts. Silencing studies showed that this was due to signaling via alpha2beta1 integrins in osteoblasts on the substrate surface and paracrine action of secreted Dkk2. Thus, human MSCs are sensitive to substrate properties that induce osteoblastic differentiation; osteoblasts interact with these surface properties via alpha2beta1 and secrete Dkk2, which acts on distal MSCs.
微结构化和高表面能钛基体可增加体内骨整合。在体外，成骨细胞分化增加，但表面直接对多能间充质干细胞（MSCs）的影响以及植入物周围环境中对 MSCs 的影响尚不清楚。我们评估了人 MSCs 对基底表面特性的反应，并研究了所涉及的潜在机制。当在微结构化 Ti 上生长时，MSCs 表现出成骨细胞特征（碱性磷酸酶、RUNX2 和骨钙素）；随着亲水性的增加，这种效果更加显著。在微结构化 Ti 上生长的成骨细胞产生的因子足以诱导共培养的 MSC 分化为成骨细胞。沉默研究表明，这是由于基质表面上成骨细胞中α2β1 整联蛋白的信号转导和分泌的 Dkk2 的旁分泌作用。因此，人 MSCs 对诱导成骨细胞分化的基底特性敏感；成骨细胞通过α2β1 与这些表面特性相互作用，并分泌 Dkk2，后者作用于远端 MSCs。
