TrabecuJar bone dynamics and bone marrow cell development in bone loss due to immobilization-unloading.

骨骼卸载在人类和动物中引起负载骨中的骨损失。我们测试了这样一个假设，即机械卸载促进骨髓细胞中细胞周期和凋亡的重要调节因子p53的信号传导，从而减少骨小梁体积。我们在尾悬p53 null p53（-/-）和野生型p53（+/+）小鼠中进行了组织形态计量学分析和骨髓细胞培养。将8周龄雄性小鼠驯化1周后随机分为4组：p53（+/+）+地面对照组（GC）、p53（+/+）+尾吊组（TS）、p53（-/-）+GC组和p53（-/-）+TS组。双侧胫骨样本用于分析。p53（+/+）+GC组与p53（+/+）+GC组之间的小梁结构、形成和吸收的组织形态计量学参数无差异。在TS一周后，p53（+/+）+TS小鼠的松质骨体积显著减少至p53（+/+）+GC组的45%。相反，p53（-/-）+TS小鼠的骨体积保持在相同的水平。 关于我们 与p53（-/-）+GC组比较差异无统计学意义。p53（+/+）+TS小鼠的骨形成率显著降低，而p53（-/-）+TS小鼠的骨形成率无显著降低。在骨髓细胞培养中，p53（+/+）+TS小鼠的碱性磷酸酶（ALP）阳性集落形成单位（CFU-f）和矿化结节数明显减少，而p53（-/-）+TS小鼠的CFU-f和矿化结节数无明显变化。流式细胞仪细胞周期分析显示，卸载后p53（+/+）小鼠骨髓细胞亚倍体比例明显高于p53（+/+）+GG小鼠，但p53（-/-）+TS和p53（-/-）+GC小鼠骨髓细胞倍体比例无明显差异。TS后p53（+/+）小鼠骨髓细胞p53和p21 mRNA表达增强。我们的数据表明，在p53（-/-）小鼠TS后，骨小梁质量和骨形成得以保留，这与从p53（-/-）小鼠体内获得的骨髓培养物中ALP阳性CFU-f和矿化结节形成密切相关。我们推测，由于机械卸载引起的骨丢失可能与细胞内p53-p21信号转导的促进有关。少

Skeletal unloading induces bone loss in loaded bones in humans and animals. We tested the hypothesis that mechanical unloading facilitates signaling of p53, an important modulator of cell cycling and apoptosis, in bone marrow cells, thereby reduces trabecular bone volume. We performed histomorphometric analyses and bone marrow cell cultures in tail-suspended p53 null p53(-/-) and wild-type p53(+/+) mice. Eight-week-old male mice were assigned to four groups as follows, after acclimatization for one week : p53(+/+)+ground control (GC), p53(+/+)+tail-suspension (TS), p53(-/-)+GC, and p53(-/-)+TS. Bilateral tibial samples were used for analysis. The histomorphometric parameters of trabecular structure, formation and resorption did not differ between the p53(+/+)+GC and p53(+/+)+GC groups. Trabecular bone volume in p53(+/+)+TS mice was significantly reduced to 45% of that in the p53(+/+)+GC group after one week of TS. In contrast, bone volume in p53(-/-)+TS mice was preserved at the same l … More evel as that in the p53(-/-)+GC group. The bone formation rate was significantly reduced in p53(+/+)+TS but not in p53(-/-)+TS mice. In bone marrow cell culture, the numbers of alkaline phosphatase (ALP)-positive colony-forming units-fibroblastic (CFU-f) and mineralized nodules were significantly reduced in p53(+/+)+TS, but not p53(-/-)+TS mice. Flow cytometric cell cycle analysis revealed that unloading significantly increased the percentage of hypoploid bone marrow cells in p53(+/+) mice relative to that in p53(+/+)+GG mice, but there was no significant difference in ploidy between p53(-/-)+TS and p53(-/-)+GC mice. p53 and p21 mRNA expression was enhanced after TS in bone marrow cells from p53(+/+) mice. Our data demonstrate that trabecular bone mass and bone formation were preserved after TS in p53(-/-) mice, closely associated with ALP-positive CFU-f and mineralized nodule formation in marrow cultures obtained from tibiae of p53(-/-) mice. We speculate that bone loss due to mechanical unloading may be related to facilitation of intracellular p53-p21 signaling. Less