Weyts F A A, Bosmans B, Niesing R, van Leeuwen J P T M, Weinans H
Department of Orthopaedics, Room Ee 1614, P.O. Box 1738, Erasmus University Medical Center Rotterdam, The Netherlands.
Calcif Tissue Int. 2003 Apr;72(4):505-12. doi: 10.1007/s00223-002-2027-0. Epub 2003 Jan 21.
Bone cells respond to mechanical stimulation. This is thought to be the mechanism by which bone adapts to mechanical loading. Reported responses of bone cells to mechanical stimuli vary widely and therefore there is no consensus on what mechanisms of mechanotransduction are physiologically relevant. We hypothesize that the differentiation stage of osteoblastic cells used to study responses to strain in vitro determines the outcome of applied loading. A human fetal osteoblast cell line was triggered to differentiate in culture to the advanced state of mineralization by addition of the osteogenic factors dexamethasone and b-glycerophosphate. Osteoblast cultures were subjected to increasing levels of cyclic, equibiaxial stretch at different stages of differentiation. We show that differentiation of human osteoblasts affects their responses to stretch in vitro. In 7-day osteoblast cultures, stretch results in decreased cell numbers as cells are triggered into apoptosis, independent of the stretch level (between 0.4-2.5%). In more mature cultures, apoptosis is not affected by the same treatment. Stretching differentiating cultures at day 14 actually increases proliferation. This is the first study reporting on differentiation-dependent mechanical control of osteoblast proliferation and apoptosis and is fundamental in understanding mechanotransduction processes in bone. The tight regulation of these responses by differentiation implies the significance of the differentiation stage of osteoblasts for the translation of mechanical signals and corroborates with the putative role of the osteoblastic lineage as mechanotransducer in bone.
骨细胞对机械刺激有反应。这被认为是骨骼适应机械负荷的机制。据报道，骨细胞对机械刺激的反应差异很大，因此对于哪些机械转导机制在生理上具有相关性尚无共识。我们假设，用于研究体外对应变反应的成骨细胞的分化阶段决定了施加负荷的结果。通过添加成骨因子地塞米松和β-甘油磷酸酯，诱导人胎儿成骨细胞系在培养中分化至矿化的晚期状态。在不同分化阶段，对成骨细胞培养物施加逐渐增加水平的循环等双轴拉伸。我们表明，人成骨细胞的分化会影响其在体外对应变的反应。在7天的成骨细胞培养物中，拉伸会导致细胞数量减少，因为细胞被触发进入凋亡，这与拉伸水平无关（在0.4 - 2.5%之间）。在更成熟的培养物中，相同处理不会影响凋亡。在第14天对分化中的培养物进行拉伸实际上会增加增殖。这是第一项报道成骨细胞增殖和凋亡的分化依赖性机械控制的研究，对于理解骨骼中的机械转导过程至关重要。分化对这些反应的严格调节意味着成骨细胞的分化阶段对于机械信号转导的重要性，并证实了成骨细胞谱系作为骨骼中机械转导器的假定作用。
