Selective estrogen receptor modulation prevents scoliotic curve progression: radiologic and histomorphometric study on a bipedal C57Bl6 mice model
Selective estrogen receptor modulation prevents scoliotic curve progression: radiologic and histomorphometric study on a bipedal C57Bl6 mice model
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DOI：
10.1007/s00586-013-3072-2
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发表时间：
2014-02-01
影响因子：
2.8
通讯作者：
Acaroglu, Emre
中科院分区：
文献类型：
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作者：
Demirkiran, Gokhan;Dede, Ozgur;Acaroglu, Emre
先前的工作表明，在松果体切除的鸡和双足C57BL6小鼠模型中，他莫昔芬治疗可以预防和逆转实验性脊柱侧凸曲线的进展。雷洛昔芬是另一种选择性雌激素受体调节剂（SERM），对骨具有雌激素激动剂作用，可增加骨密度，但对人体的副作用较少。为探讨SERM治疗能否预防C57 BL 6小鼠脊柱侧凸的进展及其机制，将80只C57 BL 6小鼠分为三苯氧胺（Tamoxifen，TMX）组、雷洛昔芬（Raloxifene，RLX）组和对照组。TMX和RLX组口服TMX和RLX 40周。在第20周和第40周进行前后位X线成像和组织形态计量学分析，在第20周，TMX和RLX组显示出更高的比率（p = 0.033，p = 0.029）和更大的弯曲幅度（p = 0.018）。在第40周，两组的曲线率相似，但TMX和RLX组的曲线幅度较小（p = 0.001）。组织形态计量学显示，接受治疗的动物具有更高的小梁密度（p = 0.04）、更低的椎间盘总体积（p = 0.038）和生长板体积（p = 0.005）以及更小的椎体（p = 0.016）。TMX或RLX治疗并未降低脊柱侧弯的发生率，但在40周时降低了弯曲幅度。与弯曲幅度降低相关的潜在机制可能是生长板的早期成熟，从而可能导致脊柱生长速率的减慢和骨密度的增加。RLX在预防褪黑激素缺乏的双足小鼠脊柱侧凸曲线进展方面与TMX一样有效。
Previous work has suggested that progression of experimental scoliotic curves in pinealectomized chicken and bipedal C57BL6 mice models may be prevented and reversed with Tamoxifen treatment. Raloxifene is another Selective Estrogen Receptor Modulator (SERM) with estrogen agonist effects on bone and increases bone density but with fewer side effects on humans. To investigate whether scoliosis progression in bipedal C57Bl6 mice model could be prevented with SERM treatment and the mechanisms associated with this effect.Eighty C57BL6 mice were rendered bipedal and divided into Tamoxifen (TMX), Raloxifene (RLX) and control groups. TMX and RLX groups received orally administered TMX and RLX for 40 weeks. Anteroposterior X-ray imaging and histomorphometric analysis (at 20th and 40th weeks) were performed.At 20th week, TMX and RLX groups displayed higher rates (p = 0.033, p = 0.029) and larger curve magnitudes (p = 0.018). At 40th week, curve rates were similar between the groups but the curve magnitudes in TMX and RLX groups were smaller (p = 0.001). Histomorphometry revealed that treated animals had higher trabecular density (p = 0.04), lower total intervertebral disc (p = 0.038) and growth plate volumes (p = 0.005) and smaller vertebral bodies (p = 0.016).Treatment with TMX or RLX did not reduce the incidence of scoliosis but decreased the curve magnitudes at 40 weeks. The underlying mechanism associated with the decrease in curve magnitudes may be the early maturation of growth plates, thereby possible deceleration of the growth rate of the vertebral column and increase in bone density. RLX is as effective as TMX in preventing the progression of scoliotic curves in melatonin deficient bipedal mice.