Kraft David C E, Bindslev Dorthe A, Melsen Birte, Abdallah Basem M, Kassem Moustapha, Klein-Nulend Jenneke
Department of Orthodontics, School of Dentistry, University of Aarhus, Aarhus, Denmark.
Eur J Oral Sci. 2010 Feb;118(1):29-38. doi: 10.1111/j.1600-0722.2009.00709.x.
For engineering bone tissue, mechanosensitive cells are needed for bone (re)modelling. Local bone mass and architecture are affected by mechanical loading, which provokes a cellular response via loading-induced interstitial fluid flow. We studied whether human dental pulp-derived mesenchymal stem cells (PDSCs) portraying mature (PDSC-mature) or immature (PDSC-immature) bone cell characteristics are responsive to pulsating fluid flow (PFF) in vitro. We also assessed bone formation by PDSCs on hydroxyapatite-tricalcium phosphate granules after subcutaneous implantation in mice. Cultured PDSC-mature exhibited higher osteocalcin and alkaline phosphatase gene expression and activity than PDSC-immature. Pulsating fluid flow (PFF) stimulated nitric oxide production within 5 min by PDSC-mature but not by PDSC-immature. In PDSC-mature, PFF induced prostaglandin E(2) production, and cyclooxygenase 2 gene expression was higher than in PDSC-immature. Implantation of PDSC-mature resulted in more osteoid deposition and lamellar bone formation than PDSC-immature. We conclude that PDSCs with a mature osteogenic phenotype are more responsive to pulsating fluid shear stress than osteogenically immature PDSCs and produce more bone in vivo. These data suggest that PDSCs with a mature osteogenic phenotype might be preferable for bone tissue engineering to restore, for example, maxillofacial defects, because they might be able to perform mature bone cell-specific functions during bone adaptation to mechanical loading in vivo.
对于工程化骨组织而言，骨（再）建模需要机械敏感细胞。局部骨量和结构受机械负荷影响，机械负荷通过负荷诱导的组织液流动引发细胞反应。我们研究了具有成熟（PDSC-成熟）或未成熟（PDSC-未成熟）骨细胞特征的人牙髓间充质干细胞（PDSCs）在体外是否对脉动流体流动（PFF）有反应。我们还评估了PDSCs在皮下植入小鼠后在羟基磷灰石-磷酸三钙颗粒上的骨形成情况。培养的PDSC-成熟细胞比PDSC-未成熟细胞表现出更高的骨钙素和碱性磷酸酶基因表达及活性。脉动流体流动（PFF）在5分钟内刺激PDSC-成熟细胞产生一氧化氮，但不刺激PDSC-未成熟细胞。在PDSC-成熟细胞中，PFF诱导前列腺素E(2)的产生，且环氧化酶2基因表达高于PDSC-未成熟细胞。植入PDSC-成熟细胞比植入PDSC-未成熟细胞导致更多类骨质沉积和板层骨形成。我们得出结论，具有成熟成骨表型的PDSCs比成骨未成熟的PDSCs对脉动流体剪切应力更敏感，且在体内产生更多骨。这些数据表明，具有成熟成骨表型的PDSCs可能更适合用于骨组织工程以修复例如颌面缺损，因为它们可能能够在体内骨适应机械负荷过程中执行成熟骨细胞特异性功能。
