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首页> 外文期刊>Scientific reports. >Radial shock waves prevent growth retardation caused by the clinically used drug vismodegib in ex vivo cultured bones
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Radial shock waves prevent growth retardation caused by the clinically used drug vismodegib in ex vivo cultured bones

机译：径向冲击波防止临床用药VISMODEGIB引起的生长迟缓在exVivo培养的骨骼中

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In childhood medulloblastoma patients, the hedgehog antagonist vismodegib is an effective anti-cancer treatment but unfortunately induces irreversible growth arrests and growth impairment limiting its use in skeletally immature patients. We hypothesized that radial shock wave treatment (rSWT) may protect drug-induced growth impairment owing to its osteogenic effects. Fetal rat metatarsal bones were exposed to vismodegib (day 0–5; 100?nM) and/or rSWT (single session); other bones from day 1 were?continuously exposed to a Gli1 antagonist (GANT61; 10?μM) and/or rSWT (single session). Control bones were untreated. The bone length was measured at intervals; histomorphometric analysis and immunostaining for PCNA, Gli1, and Ihh were performed on the sectioned bones. Bones treated with vismodegib showed impaired bone growth, reduced height of the resting-proliferative zone and reduced hypertrophic cell size compared to control. In vismodegib treated bones, a single session of rSWT partially rescued bone growth, increased the growth velocity, hypertrophic cell size, and restored growth plate morphology. Bones exposed to GANT61 showed impaired bone growth and disorganized growth plate while when combined with rSWT these effects were partially prevented. Locally applied rSWT had a chondroprotective effect in rat metatarsal bones and suggest a novel strategy to prevent growth impairment caused by vismodegib.
机译：在儿童Medulloblastoma患者中，刺猬拮抗剂Vismodegib是一种有效的抗癌治疗，但不幸的是诱导不可逆的生长逮捕和增长障碍限制其在骨骼未成熟患者中的使用。我们假设径向冲击波处理（RSWT）可能会保护药物诱导的生长损害，由于其骨质骨质作用。胎儿大鼠跖骨骨骨暴露于Vismodegib（第0-5天; 100？NM）和/或RSWT（单一会议）;第1天的其他骨骼是？连续地暴露于GLI1拮抗剂（GANT61; 10？μm）和/或RSWT（单一会议）。控制骨骼未经处理。骨长以间隔测量;对PCNA，GLI1和IHH的组织素质分析和免疫染色在切骨上进行。用Vismodegib治疗的骨骼显示出骨生长受损，静止增殖区的高度降低，与对照相比降低的肥厚细胞尺寸。在Vismodegib处理的骨骼中，单一的RSWT部分抢救骨生长，增加生长速度，肥厚细胞尺寸和恢复的生长板形态。暴露于甘墩61的骨骼显示骨生长和混乱生长板的损伤，而当与RSWT结合时，这些效果被部分地防止。当地施用的RSWT在大鼠跖骨骨骼中具有软骨保护作用，并提出了一种新的策略，以防止Vismodegib引起的增长障碍。

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