Sequential expression of bone morphogenetic protein, tumor necrosis factor, and their receptors in bone-forming reaction after mouse femoral marrow ablation
Sequential expression of bone morphogenetic protein, tumor necrosis factor, and their receptors in bone-forming reaction after mouse femoral marrow ablation
复制标题
DOI：
10.1016/s8756-3282(98)00086-6
复制
发表时间：
1998-08-01
期刊：
影响因子：
4.1
通讯作者：
Takaoka, K
中科院分区：
文献类型：
--
作者：
Shimizu, T;Mehdi, R;Takaoka, K
肿瘤坏死因子-α(TNF-α)被认为是骨吸收的促进剂和成骨的抑制因子，骨形态发生蛋白(BMP)是骨形成的促进剂。本研究对骨髓切除后骨髓腔内骨形态发生蛋白受体(BMP)、骨形态发生蛋白受体(BMPR)、肿瘤坏死因子受体(TNFR)和肿瘤坏死因子受体(TNFR)的表达模式进行了评价，并进行了免疫组织化学、原位杂交和TRAP染色。第4天，原位杂交检测到生长中的未分化细胞中的BMP-4信使核糖核酸，第7天，覆盖大量编织骨的成骨细胞也表达BMP-4。BMPR-IA和BMPR-II在消融后第4~10天呈免疫阳性，在消融后第21天和28天呈阴性，在消融后10天仅见破骨细胞。肿瘤坏死因子-α的表达在消融后一过性消失，然后在第7天重新出现，主要出现在成骨细胞中，在第7、10和14天，在编织骨的成骨细胞中观察到TNFR-I的免疫染色，后来消失。在整个反应过程中，在成骨细胞上没有观察到TNFR-II染色的证据。从第14天开始，新形成的骨量减少，并被造血细胞取代，到第28天，骨髓已再生到原始状态。本研究表明，肿瘤坏死因子-α是由成骨细胞产生和分泌的，并以自分泌的方式作用于这些细胞，从而抑制成骨功能。肿瘤坏死因子-AR也可能在破骨细胞的招募中发挥作用，因为TRAP阳性的破骨细胞在肿瘤坏死因子-α表达之后出现，(bone 23：127-133；1998)(C)1998，由Elsevier Science Inc.
Tumor necrosis factor-alpha (TNF-alpha) is considered a promoter of bone resorption and a suppressor of osteogenesis, whereas bone morphogenetic protein (BMP) is a promoter of bone formation. In the present study, the osteogenic potential of the medullary cavity after bone marrow ablation was evaluated in association with the pattern of BMP, bone morphogenetic protein receptor (BMPR), TNF-alpha, and tumor necrosis factor receptor (TNFR) expression, Immunostaining, in situ hybridization, and TRAP staining were performed following marrow ablation, By day 4, BMP-4 mRNA mas detected by in situ hybridization in growing undifferentiated cells and, on day 7, the osteoblastic cells that covered abundant woven bone also showed evidence of BMP-4 expression. BMPR-IA and BMPR-II were immunolocalized from days 4 to 10 after ablation, and became negative on days 21 and 28, At 10 days postablation, osteoclasts mere revealed by TRAP staining. TNF-alpha expression disappeared transiently after ablation and then reappeared on day 7, predominantly in osteoblastic cells, On days 7, 10, and 14, immunostaining for TNFR-I was observed in osteoblasts lining the woven bone and later disappeared. No evidence of TNFR-II staining was observed on osteoblastic cells throughout the reaction. From day 14, newly formed bone decreased in quantity and was replaced by hematopoietic cells and, by day 28, the bone marrow had regenerated to its original state, This study suggests that TNF-alpha is produced and secreted by the osteoblast and acts on these cells in an autocrine manner to suppress osteoblastic function. TNF-ar may also play a role in the recruitment of osteoclasts because TRAP-positive osteoclasts appeared after TNF-alpha expression, (Bone 23:127-133; 1998) (C) 1998 by Elsevier Science Inc. All rights reserved.