Effects of prostaglandin E2 and risedronate administration on cancellous bone in older female rats.
Effects of prostaglandin E2 and risedronate administration on cancellous bone in older female rats.
复制标题
前列腺素 E2 和利塞膦酸盐给药对老年雌性大鼠松质骨的影响。
作者：
Lin,BY;Jee,WS;Ma,YF;Ke,HZ;Kimmel,DB;Li,XJ
研究了前列腺素 E2 (PGE2) 和利塞膦酸盐 (Ris) 单独和组合 (PGE2+ Ris) 对完整老年雌性大鼠骨骼的影响，以确定 PGE2 与抗再吸收剂的组合是否比单独使用 PGE2 更有效。九个月大的 Sprague-Dawley 大鼠皮下注射媒介物、每天 6 mg PGE2/kg、每周两次 1 或 5 μg Ris/kg，或每天 6 mg PGE2/kg 加每周两次 1 或 5 μg Ris/kg（PGE2+ 1 Ris 或 PGE2+ 5 Ris），持续 60 天。治疗后，我们通过检查双荧光标记后未脱钙的纵向切片来确定纵向骨生长率、初级海绵体（PS）的定性外观以及近端胫骨干骺端（PTM）次级海绵体（SS）的静态和动态骨组织形态计量学。这些治疗对纵向骨生长的相对影响排序如下：PGE2+ 5 Ris > PGE2+ 1 Ris = 基础 > PGE2> 1 μg Ris = 5 μg Ris = 衰老。 PS的密度排序如下：PGE2+ 5 Ris > PGE2+ 1 Ris = PGE2= 5 μg Ris = 1 μg Ris > 基础 = 老化。 PS 密度的增加是刺激纵向生长和双磷+膦酸盐作用的结果。 SS 中的骨量排序如下：PGE2+ 5 Ris = PGE2+ 1 Ris = PGE2> 5 μg Ris = 1 μg Ris = 老化 = 基础。然而，单独的PGE2及其与Ris的联合治疗通过不同的组织机制积累骨。单独使用 PGE2 时，激活频率增加 8.3 倍，形成吸收比增加 1.3 倍，从而产生新骨。 PGE2和Ris的组合降低了激活频率（-54%至-74%）、骨形成率（基于组织的-31%和基于骨的-42%）和侵蚀表面（-79%至-81%），从而比单独的PGE2增加了形成吸收比（三至四倍）。增加的比率主要是由于侵蚀周长比标记周长的减少幅度更大。这项研究的主要发现是，当软骨内骨化活跃时，PGE2 和双膦酸盐 (Ris) 的组合比单独的 PGE2 或 Ris 具有更强的合成代谢能力，但在没有软骨内骨化的老骨中，PGE2+ Ris 的合成代谢能力并不比单独的 PGE2 更强。然而，PGE2alone 和 PGE2+ Ris 治疗积累骨的组织机制不同，后者允许相同的骨量以较低水平的细胞募集和活性积累。
The effects of Prostaglandin E2(PGE2) and Risedronate (Ris) both separately and in combination (PGE2+ Ris) were studied on the intact aged female rat skeleton to determine whether the combination of PGE2with an antiresorptive agent is more effective anabolically than PGE2alone. Ninemonth-old Sprague-Dawley rats were injected subcutaneously either with vehicle, 6 mg PGE2/kg per day, 1 or 5 μg Ris/kg twice a week, or 6 mg PGE2/kg per day plus 1 or 5 μg Ris/kg twice a week (PGE2+ 1 Ris or PGE2+ 5 Ris) for 60 days. After the treatment, we determined the longitudinal bone growth rate, the qualitative appearance of the primary spongiosa (PS), and the static and dynamic bone histomorphometry of the secondary spongiosa (SS) of the proximal tibial metaphysis (PTM) by examining undecalcified longitudinal sections after double-fluorescent labeling. The relative effects of these treatments on longitudinal bone growth were ranked as follows: PGE2+ 5 Ris > PGE2+ 1 Ris = basal > PGE2> 1 μg Ris = 5 μg Ris = aging. The density of the PS was ranked as follows: PGE2+ 5 Ris > PGE2+ 1 Ris = PGE2= 5 μg Ris = 1 μg Ris > basal = aging. The increase in density of the PS was the result of stimulated longitudinal growth and the action of bisphos + phonate. Bone mass in the SS was ranked as follows: PGE2+ 5 Ris = PGE2+ 1 Ris = PGE2> 5 μg Ris = 1 μg Ris = aging = basal. However, PGE2alone and its cotreatment with Ris accumulated bone by different tissue mechanisms. PGE2alone created new bone by increasing activation frequency 8.3-fold and the formation to resorption ratio 1.3-fold from the controls. The combination of PGE2and Ris depressed activation frequency (−54% to −74%), and bone formation rate (tissue-based −31%, and bone-based −42%) and eroded surface (−79% to −81%), so as to increase the formation to resorption ratio (three- to four-fold) over PGE2alone. The increased ratio was due primarily to a greater decrease in eroded perimeter than in labeled perimeter. The major finding of this study is that the combination of PGE2and a bisphosphonate (Ris) is more anabolic than PGE2or Ris alone when endochondral ossification is active, but PGE2+ Ris is no more anabolic than PGE2alone in old bone without endochondral ossification. However, the tissue mechanisms by which PGE2alone and PGE2+ Ris treatments accumulated bone differed in that the latter allowed the same bone mass to accumulate with lower levels of cell recruitment and activity.