DEFECTIVE BONE REPAIR IN MAST CELL DEFICIENT MICE WITH C-KIT LOSS OF FUNCTION
DEFECTIVE BONE REPAIR IN MAST CELL DEFICIENT MICE WITH C-KIT LOSS OF FUNCTION
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DOI：
10.22203/ecm.v028a14
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发表时间：
2014-07-01
影响因子：
3.1
通讯作者：
Martineau, P. A.
中科院分区：
文献类型：
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作者：
Behrends, D. A.;Cheng, L.;Martineau, P. A.
KitW-sh小鼠携带干细胞因子受体编码基因的失活突变，该基因在造血祖细胞表面高水平表达。这种突变导致肥大细胞缺陷，各种先天免疫缺陷，以及难以确定的骨骼异常。本研究旨在利用高分辨率显微计算机断层成像和组织学分析来描述骨骼成熟的KitW-sh小鼠皮质窗缺陷的愈合情况。所有野生型小鼠的皮质骨缺损都完全愈合，但大约一半的KitW-sh小鼠在术后12周仍未愈合。愈合不良与纤维骨髓内TRAP阳性细胞过早过度表达有关，但ALP活性变化不大。免疫组织化学显示术后1周和2周CD34阳性血管内皮细胞和F4/80阳性巨噬细胞减少。因此，KitW-sh小鼠的骨骼愈合障碍归因于分解代谢活动的改变，血管再形成的障碍，以及用致密骨编织的置换的损害。
KitW-sh mice carry an inactivating mutation in the gene encoding the receptor for stem cell factor, which is expressed at high levels on the surface of haematopoietic precursor cells. The mutation results in mast cell deficiency, a variety of defects in innate immunity and poorly defined abnormalities in bone. The present study was designed to characterise healing of a cortical window defect in skeletally mature KitW-sh mice using high-resolution micro computed tomographic imaging and histological analyses. The cortical bone defect healed completely in all wild type mice but failed to heal in about half of the KitW-sh mice by 12 weeks post-operative. Defective healing was associated with premature and excessive expression of TRAP positive cells embedded in fibrous marrow but with little change in ALP activity. Immuno-histochemical analyses revealed reduced CD34 positive vascular endothelial cells and F4/80 positive macrophages at 1 and 2 weeks post-operative. Impaired bone healing in the KitW-sh mice was therefore attributed to altered catabolic activity, impaired re-vascularisation and compromised replacement of woven with compact bone.