Influence of bisphosphonate treatment on medullary macrophages and osteoclasts: an experimental study.

Bone Marrow Research Pub Date : 2012-01-01 Epub Date: 2012-09-13 DOI:10.1155/2012/526236
Natalia Daniela Escudero, Patricia Mónica Mandalunis
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引用次数: 12

Abstract

Nitrogen-containing bisphosphonates are widely used for treating diverse bone pathologies. They are anticatabolic drugs that act on osteoclasts inhibiting bone resorption. It remains unknown whether the mechanism of action is by decreasing osteoclast number, impairing osteoclast function, or whether they continue to effectively inhibit bone resorption despite the increase in osteoclast number. There is increasing evidence that bisphosphonates also act on bone marrow cells like macrophages and monocytes. The present work sought to evaluate the dynamics of preosteoclast fusion and possible changes in medullary macrophage number in bisphosphonate-treated animals. Healthy female Wistar rats received olpadronate, alendronate, or vehicle during 5 weeks, and 5-bromo-2-deoxyuridine (BrdU) on day 7, 28, or 34 of the experiment. Histomorphometric studies were performed to study femurs and evaluate: number of nuclei per osteoclast (N.Nu/Oc); number of BrdU-positive nuclei (N.Nu BrdU+/Oc); percentage of BrdU-positive nuclei per osteoclast (%Nu.BrdU+/Oc); medullary macrophage number (mac/mm(2)) and correlation between N.Nu/Oc and mac/mm(2). Results showed bisphosphonate-treated animals exhibited increased N.Nu/Oc, caused by an increase in preosteoclast fusion rate and evidenced by higher N.Nu BrdU+/Oc, and significantly decreased mac/mm(2). Considering the common origin of osteoclasts and macrophages, the increased demand for precursors of the osteoclast lineage may occur at the expense of macrophage lineage precursors.

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双膦酸盐处理对骨髓巨噬细胞和破骨细胞影响的实验研究。
含氮双膦酸盐被广泛用于治疗各种骨病变。它们是抗代谢药物,作用于破骨细胞,抑制骨吸收。其作用机制是通过减少破骨细胞数量,损害破骨细胞功能,还是在破骨细胞数量增加的情况下继续有效抑制骨吸收,目前尚不清楚。越来越多的证据表明,双膦酸盐也作用于骨髓细胞,如巨噬细胞和单核细胞。本研究旨在评估二磷酸盐处理动物中破骨前细胞融合的动态和髓质巨噬细胞数量的可能变化。健康雌性Wistar大鼠在5周内接受奥帕膦酸盐、阿仑膦酸盐或代药,并在实验的第7、28、34天接受5-溴-2-脱氧尿苷(BrdU)。对股骨进行组织形态学研究,并评估:每个破骨细胞的细胞核数(N.Nu/Oc);BrdU阳性核数(N.Nu BrdU+/Oc);每个破骨细胞brdu阳性细胞核百分比(%Nu.BrdU+/Oc);骨髓巨噬细胞数量(mac/mm(2))及N.Nu/Oc与mac/mm(2)的相关性。结果显示,双膦酸盐处理的动物由于破骨前细胞融合率的增加,N.Nu/Oc增加,N.Nu BrdU+/Oc增加,mac/mm显著降低(2)。考虑到破骨细胞和巨噬细胞的共同起源,对破骨细胞谱系前体的需求增加可能以牺牲巨噬细胞谱系前体为代价。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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