The influence of mechanical stress on the gene expression related to the differentiation and the growth of bone cell

为了研究物理刺激6N对骨重建的影响，我们利用机械应力模型，研究了成骨细胞NO的产生以及NOS、COX-2和MAPKs的表达和/或激活。此外，还利用ELISA对核因子受体激活剂B配体(RANKL)和骨保护素(OPG)的合成进行了研究。结论：1.对成骨细胞施加机械应力(循环拉伸应变)可诱导NO的产生和iNOS mRNA1的表达。定量RT-PCR法检测，机械应激可使COX-2mRNA表达增加。但细胞因子及其受体的mRNA表达无明显变化。P38MAPK在施加机械应力后即被激活，而ERK1/2和JNK未被激活。机械应激3天后，p38MAPK活性保持不变，ERK1/2活性逐渐下调。每天4h的机械应力作用3d，sRANKL释放减少，OPG合成增加，提示机械应力可激活成骨细胞中的p38MAPK。结果表明，机械应力通过激活p38MAPK诱导成骨细胞产生NO、COX-2mRNA和OPG的表达。提示机械应力可增强成骨细胞形成新骨的功能。

To study the influence of physical stimulus 6n bone remodeling, using a model of mechanical stress on osteoblasts, we investigated the production of NO and the expression and/or activation of NOS, Cox-2, and MAPKs. Furthermore, the synthesis of receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) were investigated by ELISA.Results were as follows.1. Mechanical stress (cyclic tensile strain) against osteoblasts induced the NO production and the expression for iNOS mRNA.2. By the quantitative RT-PCR method, mechanical stress increased the expression for Cox-2 mRNA. But the expression of mRNA of cytokine and cytokine-receptors were not changed.3. The p38 MAPK was activated just after starting to add mechanical stress, on the contrary, ERK1/2 and JNK were not activated. Mechanical stress for 3 days, p38 MAPK activation was kept and ERK1/2 activation was down-regulated day by day.4. Adding mechanical stress at 4 hrs a day for 3days, sRANKL release was decreased and OPG synthesis was increased, simultaneously.These results suggested that p38 MAPK in osteoblasts was activated by adding mechanical stress. It was revealed consequently that mechanical stress activated osteoblasts to induce NO production, expression for Cox-2 mRNA and OPG through p38 MAPK activation. It was suggested that mechanical stress might enhance the function of osteoblasts to form new bone.