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Regulation and Biological Significance of Formation of Osteoclasts and Foreign Body Giant Cells in an Extraskeletal Implantation Model

机译:骨骼外植入模型中破骨细胞和异物巨细胞形成的调控及其生物学意义

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摘要

The implantation of biomaterials induces a granulomatous reaction accompanied by foreign body giant cells (FBGCs). The characterization of multinucleated giant cells (MNGCs) around bone substitutes implanted in bone defects is more complicated because of healing with bone admixed with residual bone substitutes and their hybrid, and the appearance of two kinds of MNGCs, osteoclasts and FBGCs. Furthermore, the clinical significance of osteoclasts and FBGCs in the healing of implanted regions remains unclear. The aim of the present study was to characterize MNGCs around bone substitutes using an extraskeletal implantation model and evaluate the clinical significance of osteoclasts and FBGCs. Beta-tricalcium phosphate (β-TCP) granules were implanted into rat subcutaneous tissue with or without bone marrow mesenchymal cells (BMMCs), which include osteogenic progenitor cells. We also compared the biological significance of plasma and purified fibrin, which were used as binders for implants. Twelve weeks after implantation, osteogenesis was only detected in specimens implanted with BMMCs. The expression of two typical osteoclast markers, tartrate-resistant acid phosphatase (TRAP) and cathepsin-K (CTSK), was analyzed, and TRAP-positive and CTSK-positive osteoclasts were only detected beside bone. In contrast, most of the MNGCs in specimens without the implantation of BMMCs were FBGCs that were negative for TRAP, whereas the degradation of β-TCP was detected. In the region implanted with β-TCP granules with plasma, FBGCs tested positive for CTSK, and when β-TCP granules were implanted with purified fibrin, FBGCs tested negative for CTSK. These results showed that osteogenesis was essential to osteoclastogenesis, two kinds of FBGCs, CTSK-positive and CTSK-negative, were induced, and the expression of CTSK was plasma-dependent. In addition, the implantation of BMMCs was suggested to contribute to osteogenesis and the replacement of implanted β-TCP granules to bone.
机译:生物材料的植入会引起肉芽肿反应,并伴有异物巨细胞(FBGC)。由于将骨与残留的骨替代物及其混合体混合,从而愈合,并且出现了两种MNGC(破骨细胞和FBGC),因此,植入骨缺损中的骨替代物周围的多核巨细胞(MNGC)的特征更加复杂。此外,破骨细胞和FBGCs在植入区域愈合中的临床意义仍不清楚。本研究的目的是使用骨骼外植入模型表征骨替代物周围的MNGC,并评估破骨细胞和FBGC的临床意义。将β-磷酸三钙(β-TCP)颗粒植入有或没有骨髓间充质细胞(BMMC)的大鼠皮下组织中,其中包括成骨祖细胞。我们还比较了血浆和纯化的纤维蛋白的生物学意义,这些蛋白和纤维蛋白被用作植入物的粘合剂。植入后十二周,仅在植入BMMC的标本中检测到成骨作用。分析了两种典型的破骨细胞标志物,酒石酸抗性酸性磷酸酶(TRAP)和组织蛋白酶K(CTSK)的表达,仅在骨旁检测到TRAP阳性和CTSK阳性破骨细胞。相反,在没有植入BMMC的标本中,大多数MNGC是FBGC,它们对TRAP呈阴性,而检测到β-TCP的降解。在植入有血浆的β-TCP颗粒的区域,FBGC对CTSK呈阳性反应,而当β-TCP颗粒与纯化的纤维蛋白植入时,FBGC对CTSK呈阴性。这些结果表明,成骨作用对于破骨细胞形成是必不可少的,诱导了两种FBGC,即CTSK阳性和CTSK阴性,并且CTSK的表达是血浆依赖性的。另外,建议将BMMC植入有助于成骨和将植入的β-TCP颗粒替换成骨。

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