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局部 rhBMP-2 注射治疗大鼠钻孔损伤:是否有全身作用?

Local rhBMP-2 injection after drill-hole injury in rats: does it have systemic effects?

机构信息

Department of Pathology, Medical School of Pamukkale University, Denizli, Turkey.

Department of Orthopaedics and Traumatology, Medical School of Pamukkale University Denizli, Turkey.

出版信息

Int J Immunopathol Pharmacol. 2014 Apr-Jun;27(2):253-60. doi: 10.1177/039463201402700212.

DOI:10.1177/039463201402700212
PMID:25004837
Abstract

The aim of this study is to investigate the histopathological findings of drill hole healing and interactions of parathyroid hormone (PTH), β-catenin and transcription factor-4 (TCF7L2/Tcf-4) after local application of recombinant human bone morphogenic protein-2 (rhBMP-2). Sprague Dawley rats were used in two groups of ‘femoral cortex hole model’. In the non-treated group, a hole was opened with a 3 mm K-wire in the distal and mid third junction of the right femur. In the treated group, local rhBMP-2 protein was injected into the similar femoral hole. Sterile 18M H2O was injected into the femoral hole at contralateral femur. There was more subperiosteal membranous bone reaction in the group treated with rhBMP-2 injection compared to the non-treated group. This was also proven immunohistochemically in both ipsilateral and contralateral femur with increased anti bone morphogenic protein-2 (anti BMP-2) expression. Moreover, there was an increased subperiosteal reaction at the contralateral femur. Also, in the treated group, PTH expression was increased in cells that form callus, and nuclear beta-catenin expression was increased in chondrocytes of periosteal ossification. Future studies should try to find whether the effects of rhBMP-2 on PTH and Wnt signaling pathway changes with different fracture models, also the systemic effects of local rhBMP-2 application should be investigated.

摘要

本研究旨在探讨局部应用重组人骨形态发生蛋白-2(rhBMP-2)后,钻孔愈合的组织病理学变化以及甲状旁腺激素(PTH)、β-连环蛋白(β-catenin)和转录因子-4(TCF7L2/Tcf-4)之间的相互作用。我们使用 Sprague Dawley 大鼠建立了“股骨皮质钻孔模型”的两组实验。在未治疗组中,在右侧股骨远端和中三分之一交界处用 3mm K 线钻开一个孔。在治疗组中,将局部 rhBMP-2 蛋白注入类似的股骨孔中。在对侧股骨的股骨孔中注入无菌 18M H2O。与未治疗组相比,rhBMP-2 注射组的骨膜下膜性骨反应更多。这在同侧和对侧股骨的免疫组织化学染色中也得到了证实,抗骨形态发生蛋白-2(抗 BMP-2)表达增加。此外,对侧股骨也出现了骨膜下反应增加。此外,在治疗组中,形成骨痂的细胞中 PTH 表达增加,骨膜成骨的软骨细胞中核β-catenin 表达增加。未来的研究应尝试确定 rhBMP-2 对 PTH 和 Wnt 信号通路的影响是否因不同的骨折模型而不同,还应研究局部 rhBMP-2 应用的全身效应。

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