Molecular basis of osteoclastogenesis induced by osteoblasts exposed to wear particles
Molecular basis of osteoclastogenesis induced by osteoblasts exposed to wear particles
复制标题
DOI：
10.1016/j.biomaterials.2004.07.045
复制
发表时间：
2005-05-01
期刊：
影响因子：
14
通讯作者：
Giunti, A
中科院分区：
文献类型：
--
作者：
Granchi, D;Amato, I;Giunti, A
在这项研究中，我们调查的分子机制，人类成骨细胞（HOB）挑战磨损碎片促进破骨细胞前体的分化。HOB从松质骨获得，并暴露于氧化铝（Al 2 O3）或“超高分子量聚乙烯”（UHMWPE）颗粒24小时。将上清液（HOB-CM）用于免疫酶法检测NF-κ B配体受体激活剂（RANKL）和骨保护素（OPG），以及用于诱导来自外周血单核细胞（PBMC）的破骨细胞分化。OPG与RANKL的比值在CPE激发的HOB的条件培养基中显著降低。形态学和细胞化学分析表明HOB-CM本身诱导破骨细胞形成，但当PBMC与1 μ g/mL UHMWPE HOB-CM一起培养时，获得大量多核抗酒石酸酸性磷酸酶（TRAP）阳性巨细胞。评价了参与破骨细胞分化和活化的基因的表达，即c-fms、RANK、c-src、c-fos、组织蛋白酶-K（CATK）、TRAP和降钙素R（CTR）。UHMWPE HOB-CM增加了c-src表达，表明聚乙烯碎片有利于HOB诱导破骨细胞极化和粘附相关通路的旁分泌活性。相反，Al 2 O3 HOB-CM下调c-fos表达，表明从巨噬细胞进入破骨细胞谱系的通道是偏离的。这些结果表明，在诱导破骨细胞分化方面，Al 2 O3磨屑的活性低于UHMWPE。此外，它们提供了对颗粒诱导破骨细胞生成的分子基础的新见解，这是计划假体周围骨质溶解的模式特异性靶向的起点。(C)2004爱思唯尔有限公司保留所有权利。
In this study, we investigate the molecular mechanisms by which human osteoblasts (HOB) challenged with wear debris promote the differentiation of osteoclast precursors. HOB were obtained from trabecular bone and exposed to alumina (Al2O3) or 'ultra-high molecular weight polyethylene' (UHMWPE) particles for 24 h. The supernatant (HOB-CM) was used for the immunoenzymatic detection of receptor activator of NF-kappaB ligand (RANKL) and osteoprotegerin (OPG), as well as for inducing the osteoclast differentiation from peripheral blood mononuclear cells (PBMC). The OPG-to-RANKL ratio was significantly decreased in the conditioned medium of UHMWPE-challenged HOB. Morphological and cytochemical analysis showed that HOB-CM induced by itself the osteoclast formation, but a large amount of multinucleated tartrate-resistant acid phosphatase (TRAP)-positive giant cells were obtained when PBMCs were cultured with I mug/mL UHMWPE HOB-CM. The expression of genes involved in osteoclast differentiation and activation was evaluated, i.e. c-fms, RANK, c-src, c-fos, cathepsin-K (CATK), TRAP, and calcitonin R (CTR). The UHMWPE HOB-CM increases c-src expression, suggesting that polyethylene debris favour the paracrine activity of HOB in inducing the pathway involved in osteoclast polarization and adhesion. On the contrary, Al2O3 HOB-CM downregulates c-fos expression, suggesting that the passage from macrophages into the osteoclast lineage is deviated. These results show that Al2O3 wear debris is less active than UHMWPE in inducing osteoclast differentiation. Moreover, they provide new insight into the molecular)basis of particle-induced osteoclastogenesis, that is the starting point for planning mode-specific targeting of periprosthetic)osteolysis. (C) 2004 Elsevier Ltd. All rights reserved.