Impaired Fracture Healing Caused by Deficiency of the Immunoreceptor Adaptor Protein DAP12.
Impaired Fracture Healing Caused by Deficiency of the Immunoreceptor Adaptor Protein DAP12.
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DOI：
10.1371/journal.pone.0128210
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Itoi E
中科院分区：
文献类型：
--
作者：
Kamimura M;Mori Y;Sugahara-Tobinai A;Takai T;Itoi E
破骨细胞在骨代谢中起重要作用，但其在骨折愈合中的确切作用尚不清楚。DAP 12是一种免疫适配蛋白，在髓系细胞（包括破骨细胞）上具有相关的免疫受体。它的缺乏会由于抑制破骨细胞的发育和活化而引起骨硬化症。在本报告中，我们使用C57 BL/6（B6）和DAP 12-/-小鼠评估了DAP 12对骨折愈合过程的影响。采用放射学、显微CT、组织学、免疫组织化学和实时RT-PCR评价愈合情况。放射学检查显示，在后期阶段，DAP 12-/-小鼠的骨痂体积较低，骨痂射线可透性较低。显微CT图像和定量结构分析表明，DAP 12-/-小鼠形成致密的小梁结构的胼胝体，并在表面上经历了恶化的皮质壳形成。在组织学上，DAP 12-/-小鼠表现出较少的软骨吸收和编织骨形成。此外，在DAP 12-/-小鼠中显著的皮质壳形成少得多。免疫组化显示F4/80阳性单核细胞和巨噬细胞侵入DAP 12-/-小鼠骨折血肿的程度较低。在DAP 12-/-小鼠中，Col 1a 1、Col 2a 1和Col 10a 1的表达水平增加，随后变得高于B6小鼠。在DAP 12-/-小鼠的早期阶段，Tnf的基因表达降低。我们的研究结果表明，DAP 12缺陷损害骨折愈合，表明DAP 12在初始炎症反应，骨重建和再生中的重要作用。
Osteoclasts play an important role in bone metabolism, but their exact role in fracture healing remains unclear. DAP12 is an immunoadaptor protein with associated immunoreceptors on myeloid lineage cells, including osteoclasts. Its deficiency causes osteopetrosis due to suppression of osteoclast development and activation. In this report, we assessed the impact of DAP12 on the fracture healing process using C57BL/6 (B6) and DAP12–/– mice. Healing was evaluated using radiography, micro-CT, histology, immunohistochemistry and real-time RT-PCR. Radiography showed lower callus volume and lower callus radiolucency in DAP12–/– mice during later stages. Micro-CT images and quantitative structural analysis indicated that DAP12–/– mice developed calluses of dense trabecular structures and experienced deteriorated cortical shell formation on the surface. Histologically, DAP12–/– mice showed less cartilaginous resorption and woven bone formation. In addition, prominent cortical shell formation was much less in DAP12–/– mice. Immunohistochemistry revealed lower invasion of F4/80 positive monocytes and macrophages into the fracture hematoma in DAP12–/– mice. The expression levels of Col1a1, Col2a1 and Col10a1 in DAP12–/– mice increased and subsequently became higher than those in B6 mice. There was a decrease in the gene expression of Tnf during the early stages in DAP12–/– mice. Our results indicate that DAP12 deficiency impairs fracture healing, suggesting a significant role of DAP12 in the initial inflammatory response, bone remodeling and regeneration.
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影响因子：
30.8
作者：
Paloneva, J;Kestilä, M;Peltonen, L
通讯作者：
Peltonen, L
影响因子：
2.8
作者：
Matos, Marcos Almeida;Tannuri, Uenis;Guarniero, Roberto
通讯作者：
Guarniero, Roberto
影响因子：
6.2
作者：
Cao, YP;Mori, S;Norimatsu, H
通讯作者：
Norimatsu, H
影响因子：
4.4
作者：
Aoki, N;Kimura, S;Katagiri, M
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Katagiri, M
影响因子：
6.2
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通讯作者：
Graves, Dana T.