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Effects of bisphosphonates on osteogenesis and osteoclastogenesis signaling during the endochondral ossification of growing rats

机译:双膦酸盐对生长大鼠骨质骨化骨化骨化骨质发生和骨质细胞发生信号的影响

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Osteoclasts and chondroclasts are necessary, during endochondral ossification, for the resorption of primary bone and calcified cartilage septa, respectively. The bisphosphonates inhibit mineralized tissue resorption by various mechanisms according to the different types of this drug, which can affect bone remodeling during skeletal growth. The objective of the present study is to analyze the way that alendronate (ALN) and etidronate (ETN) can affect osteoclastogenesis and bone formation during endochondral ossification of the long bones of growing rats. Newborn Wistar rats were treated daily with ETN, ALN, or sterile saline solution (control) for 21 days. Their femur and tibiae epiphyses were radiographed and analyzed by light, scanning and transmission electron microscopy. The expression of genes related to osteogenesis and to osteoclast differentiation and activity were analyzed by real-time quantitative polymerase chain reaction. The ETN group presented reduced body weight, disorganized growth plate and an extended area of cartilage in the ossification zone with little bone matrix; in the ALN group, this area was not altered. The ALN presented latent TRAP-positive cells, whereas in the ETN group, they were activated. The expression of NF kappa B1 and 2, OPG, Spp1 and Runx2 in the ossification zone was reduced by both bisphosphonates. RANKL expression was reduced by ETN, whereas ALN decreased the expression of RANK. The results also indicated that, in addition to the anti-resorptive effect of the drugs, disturbances in bone deposition occurred concomitantly with the reduced expression of osteogenesis-related genes.
机译:在内核骨化期间,骨核糖碱和软骨糖苷分别在初级骨和钙化软骨隔膜的吸收过程中是必要的。双膦酸盐通过根据该药物的不同类型抑制各种机制的矿化组织吸收,这可能影响骨骼生长期间的骨质重塑。本研究的目的是分析阿仑膦酸盐(ALN)和Etidronate(ETN)可以影响骨髓细胞化在生长大鼠的长骨的内核骨化期间影响骨细胞发生和骨形成的方式。新生儿Wistar大鼠每天用EtN,AlN或无菌盐水溶液(对照)治疗21天。他们的股骨和胫骨膜骨骺被射线照相和通过光,扫描和透射电子显微镜分析。通过实时定量聚合酶链反应分析与骨发生相关的基因和骨质体分化和活性的表达。 ETN组在骨基质中呈现减少体重,混乱的生长板和软骨的扩展区域;在ALN组中,该区域没有改变。 ALN呈现潜在的捕集阳性细胞,而在ETN组中,它们被激活。两种双膦酸盐酸盐酸盐酸盐区中的NF Kappa B1和2,OPG,SPP1和RUNX2的表达减少。 RANKL表达减少了ETN,而ALN降低了等级的表达。结果还表明,除了药物的抗复苏效果之外,骨沉积中的紊乱伴随着骨质发生相关基因的表达减少而发生。

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