Impaired fracture healing in macrophage migration inhibitory factor-deficient mice
Impaired fracture healing in macrophage migration inhibitory factor-deficient mice
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DOI：
10.1007/s00198-010-1385-0
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发表时间：
2011-06-01
影响因子：
4
通讯作者：
Yasuda, K.
中科院分区：
文献类型：
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作者：
Kobayashi, T.;Onodera, S.;Yasuda, K.
本研究利用MIF基因缺陷小鼠（MIF KO）研究巨噬细胞迁移抑制因子（MIF）在骨折修复中的作用。MIF KO的骨折愈合延迟，这主要是由于骨折骨痂内类骨矿化延迟。我们之前报道了巨噬细胞迁移抑制因子（MIF）在大鼠骨折愈合过程中的表达上调。然而，其在这一过程中的病理生理作用尚不清楚。本研究的目的是利用MIF基因缺陷小鼠（MIF KO）阐明MIF在骨折愈合过程中的作用。采用胫骨骨折模型研究野生型小鼠（WT）和MIF KO （n = 70）的骨修复。放射学，生物力学，组织学，骨组织形态学和分子分析进行。骨折后生物力学测试显示，在第42天，MIF KO的最大载荷和刚度明显低于WT。然而，在第84天，两组之间观察到相似的水平。骨组织形态学分析显示，与WT愈伤组织相比，MIF KO愈伤组织的类骨体积显著增加，矿物质附着率较低，破骨细胞数量较少。基质金属蛋白酶(MMP)-2、膜型1-MMP、组织蛋白酶K和组织非特异性碱性磷酸酶的信使核糖核酸表达在MIF KO愈伤组织中被显著抑制。本研究结果表明，MIF KO的骨折愈合延迟主要是由于类骨矿化的延迟。
This study investigated the role of macrophage migration inhibitory factor (MIF) in fracture repair using MIF gene-deficient mice (MIF KO). Fracture healing was delayed in MIF KO, and this was mainly due to the delay in the mineralization of osteoid within the fracture callus.We previously reported that the expression of macrophage migration inhibitory factor (MIF) was up-regulated during the fracture healing process in rats. However, its role in the pathophysiology of this process remained unclear. The aim of the present study was to clarify the role of MIF in the fracture healing process using MIF gene-deficient mice (MIF KO).Bone repair in wild-type mice (WT) and MIF KO (n = 70, respectively) was investigated using a tibia fracture model. Radiographic, biomechanical, histological, bone histomorphometric, and molecular analyses were performed.Post-fracture biomechanical testing showed that maximum load and stiffness were significantly lower in MIF KO than in WT on day 42. However, similar levels were observed between the two groups on day 84. Bone histomorphometric analysis revealed significantly higher osteoid volume, a lower mineral apposition rate, and smaller numbers of osteoclasts in the MIF KO callus compared to the WT callus. The messenger ribonucleic acid expressions of matrix metalloproteinase (MMP)-2, membranous type 1-MMP, cathepsin K, and tissue nonspecific alkaline phosphatase were found to be significantly suppressed in the MIF KO callus.The results of the present study suggest that delayed fracture healing in MIF KO was mainly attributable to a delay in osteoid mineralization.