Expression and role of interleukin-6 in distraction osteogenesis
Expression and role of interleukin-6 in distraction osteogenesis
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DOI：
10.1007/s00223-006-0240-y
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发表时间：
2007-03-01
影响因子：
4.2
通讯作者：
Choi, I. H.
中科院分区：
文献类型：
--
作者：
Cho, T. -J.;Kim, J. A.;Choi, I. H.
牵引成骨是骨愈合的一种特殊形式，其中良好控制的牵引应力和愈伤组织内随之而来的拉伸应变诱导非常有效的新骨形成。促炎细胞因子参与骨折愈合和愈伤组织重塑的早期阶段。在牵张成骨和急性延长的 Sprague-Dawley 大鼠胫骨模型中评估促炎细胞因子的时间表达模式，发现只有白介素 6 (IL-6) 在牵张阶段被特异性诱导。 IL-6 免疫反应性不仅在造血细胞和成骨细胞中检测到，还在纤维间带的纺锤形细胞中检测到，那里集中了大多数拉伸应变。体外研究表明，IL-6不影响C3H10T1/2细胞、小鼠骨髓基质细胞（MSCs）或MC3T3-E1细胞的增殖；但其阻断抗体降低了C3H10T1/2细胞和MSC的增殖。 IL-6或其阻断抗体不改变COL1A1和骨桥蛋白的mRNA表达，但IL-6使MC3T3-E1细胞的碱性磷酸酶活性增加，而其阻断抗体则降低MC3T3-E1细胞的碱性磷酸酶活性。这些发现表明，IL-6 是一种促炎细胞因子，可对牵引成骨过程中的拉伸应变做出反应。 IL-6 对原始间充质细胞的增殖产生负面影响，而在体外，IL-6 可增强更成熟的成骨细胞谱系细胞的分化。 IL-6 似乎是牵张成骨过程中引发的信号级联复杂网络中涉及的细胞因子之一，并且可能对未成熟和成熟的成骨细胞谱系细胞产生不同的影响。
Distraction osteogenesis is a special form of bone healing in which well-controlled distraction stresses and consequent tensile strains within callus tissue induce very efficient new bone formation. Proinflammatory cytokines are involved during the early phase of fracture healing and callus remodeling. Temporal expression patterns of proinflammatory cytokines were assessed in Sprague-Dawley rat tibial models of distraction osteogenesis and acute lengthening, and only interleukin-6 (IL-6) was found to be specifically induced during the distraction phase. IL-6 immunoreactivity was detected not only in hemopoietic cells and osteoblasts but also in the spindle-shaped cells of the fibrous interzone, where most of the tensile strains are concentrated. In vitro study revealed that IL-6 did not affect the proliferation of C3H10T1/2 cells, mouse bone marrow stromal cells (MSCs), or MC3T3-E1 cells; but its blocking antibody reduced the proliferation of C3H10T1/2 cells and MSCs. The mRNA expression of COL1A1 and osteopontin were not changed by IL-6 or its blocking antibody, but the alkaline phosphatase activities of MC3T3-E1 cells were increased by IL-6 and decreased by its blocking antibody. These findings indicate that IL-6 is a proinflammatory cytokine that responds to tensile strain during distraction osteogenesis. IL-6 negatively affects the proliferation of primitive mesenchymal cells, whereas the differentiation of more mature osteoblastic lineage cells is enhanced by IL-6 in vitro. IL-6 appears to be one of the cytokines involved in the complex network of signal cascades evoked during distraction osteogenesis and may differentially affect immature and mature osteoblastic lineage cells.