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

在人类和动物中，骨骼卸载会导致负载骨骼的骨质流失。我们验证了机械卸载促进p53信号传导的假设，p53是骨髓细胞周期和凋亡的重要调节剂，从而减少小梁骨体积。我们对尾巴悬浮p53 null（-/-）和野生型p53（+/+）小鼠进行了组织形态学分析和骨髓细胞培养。8周龄雄性小鼠经1周驯化后，分为4组：p53(+/+)+地面对照（GC）、p53(+/+)+悬尾（TS）、p53(-/-)+GC和p53(-/-)+TS。双侧胫骨标本用于分析。p53(+/+)+GC组和p53(+/+)+GC组小梁结构、形成和吸收的组织形态学参数无显著差异。p53(+/+)+TS组小鼠骨小梁体积在TS治疗1周后明显减少至p53(+/+)+GC组的45%，而p53(-/-)+TS组小鼠骨小梁体积与p53(-/-)+GC组保持相同的水平。p53(+/+)+TS组骨形成率显著降低，而p53(-/-)+TS组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-纤维母细胞（CFU-f）和矿化结节的数量显著减少，而p53(-/-)+TS小鼠则没有。流式细胞术细胞周期分析显示，卸荷显著增加了p53(+/+)+GG小鼠的骨髓次倍体百分比，而p53(-/-)+TS与p53(-/-)+GC小鼠的倍性差异不显著。p53（+/+）小鼠骨髓细胞经TS后p53和p21 mRNA表达增强。我们的数据表明，p53（-/-）小鼠的骨小梁骨量和骨形成在TS后得以保留，这与p53（-/-）小鼠胫骨骨髓培养物中alp阳性的CFU-f和矿化结节形成密切相关。我们推测，机械卸载导致的骨质流失可能与细胞内p53-p21信号传导的促进有关。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