Aged male rats regenerate cortical bone with reduced osteocyte density and reduced secretion of nitric oxide after mechanical stimulation.
Aged male rats regenerate cortical bone with reduced osteocyte density and reduced secretion of nitric oxide after mechanical stimulation.
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DOI：
10.1007/s00223-013-9832-5
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发表时间：
2014-05
影响因子：
4.2
通讯作者：
Goldstein SA
中科院分区：
文献类型：
--
作者：
Joiner DM;Tayim RJ;McElderry JD;Morris MD;Goldstein SA
机械负荷对骨损伤修复至关重要。骨细胞是骨中的机械传感器，并通过间隙连接通道参与信号传导，这些通道主要由连接蛋白43（Cx43）组成。一氧化氮（NO）和前列腺素E2（PGE2）对骨有合成代谢和分解代谢的作用，这些分子在机械刺激后分泌。年龄对损伤后骨组织修复以及再生骨将机械刺激转化为细胞反应能力的影响尚未被探究。本研究的目的是检查（1）老年和成年动物再生骨中的骨细胞及其矿化基质，以及（2）老年和成年动物再生骨外植体通过NO和PGE2分泌将周期性机械负荷转化为细胞反应的能力。在老年（21月龄）或成年（6月龄）雄性大鼠的骨干处制造双侧皮质缺损，并让新骨组织在一个定制的几何形状可控的植入物中生长。与成年动物相比，老年动物再生骨的矿化程度和矿物质与基质的比例显著更高，而陷窝和骨细胞密度以及磷酸化（pCx43）和总Cx43蛋白则显著更低。与老年动物相比，成年大鼠的再生骨在负荷作用下pCx43蛋白和PGE2分泌增加，NO分泌也更多。老年动物再生骨中骨细胞密度和Cx43的降低可能会限制间隙连接的形成以及负荷后NO和PGE2的分泌，从而改变体内的骨形成和骨吸收。
Mechanical loading is integral to the repair of bone damage. Osteocytes are mechanosensors in bone and participate in signaling through gap junction channels, which are primarily comprised of connexin 43 (Cx43). Nitric oxide (NO) and prostaglandin E2 (PGE2) have anabolic and catabolic effects on bone, and the secretion of these molecules occurs after mechanical stimulation. The effect of age on the repair of bone tissue after damage and on the ability of regenerated bone to transduce mechanical stimulation into a cellular response is unexplored. The goal of this study was to examine (1) osteocytes and their mineralized matrix within regenerated bone from aged and mature animals and (2) the ability of regenerated bone explants from aged and mature animals to transduce cyclic mechanical loading into a cellular response through NO and PGE2 secretion. Bilateral cortical defects were created in the diaphysis of aged (21-month-old) or mature (6-month-old) male rats, and new bone tissue was allowed to grow into a custom implant of controlled geometry. Mineralization and mineral-to-matrix ratio were significantly higher in regenerated bone from aged animals, while lacunar and osteocyte density and phosphorylated (pCx43) and total Cx43 protein were significantly lower, relative to mature animals. Regenerated bone from mature rats had increased pCx43 protein and PGE2 secretion with loading and greater NO secretion relative to aged animals. Reduced osteocyte density and Cx43 in regenerated bone in aged animals could limit the establishment of gap junctions as well as NO and PGE2 secretion after loading, thereby altering bone formation and resorption in vivo.