Genetic variation influences the skeletal response to hindlimb unloading in the eight founder strains of the diversity outbred mouse population.
Genetic variation influences the skeletal response to hindlimb unloading in the eight founder strains of the diversity outbred mouse population.
复制标题
遗传变异影响多样性远交小鼠群体的八个创始品系对后肢卸载的骨骼反应。
DOI：
10.1002/jor.25646
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发表时间：
2024
期刊：
影响因子：
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通讯作者：
Donahue,HenryJ
中科院分区：
文献类型：
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作者：
Friedman,MichaelA;Buettmann,EvanG;Zeineddine,Yasmina;Abraham,LovellB;Hoppock,GabrielA;Meas,StevenJ;Zhang,Yue;Farber,CharlesR;Donahue,HenryJ
在废用期间，机械性卸载导致广泛的骨丢失，降低骨体积和强度。骨量的变化和骨质疏松症的风险受遗传因素的影响;然而，目前尚不清楚遗传变异如何影响骨骼对卸载的反应。我们以前发现，遗传变异影响了8个杰克逊实验室J：DO创始菌株对3周固定的肌肉骨骼反应：C57 Bl/6 J、A/J、129 S1/SvImJ、NOD/ShiLtJ、NZO/HlLtJ、CAST/EiJ、PWK/PhJ和WSB/EiJ。后肢卸载（HLU）是模拟废用的局部和系统贡献者的最佳模型，因此可能对骨骼的影响比固定更大。我们假设遗传变异会影响8种创始菌株对HLU的反应。将每种建立者品系的小鼠置于HLU中3周，并分析股骨和胫骨。HLU和小鼠应变对体重、股骨小梁BV/TV和股骨极限力存在显着的相互作用。这表明卸载仅在某些小鼠品系中引起显著的分解代谢效应。C57 BL/6 J小鼠受卸载的影响最大，而其他品系的小鼠则受到更多保护。在胫骨骨代谢基因的基因表达上，HLU和小鼠品系之间存在显著的交互作用。这表明，卸载仅对某些小鼠品系的骨代谢基因产生显著影响。不同的小鼠品系对HLU的反应不同，这可以通过遗传差异来解释。这些结果表明，远交J：DO小鼠将是一个强大的模型，用于检查遗传学对骨骼对HLU的反应的影响。
During disuse, mechanical unloading causes extensive bone loss, decreasing bone volume and strength. Variations in bone mass and risk of osteoporosis are influenced by genetics; however, it remains unclear how genetic variation affects the skeletal response to unloading. We previously found that genetic variation affects the musculoskeletal response to 3 weeks of immobilization in the 8 Jackson Laboratory J:DO founder strains: C57Bl/6J, A/J, 129S1/SvImJ, NOD/ShiLtJ, NZO/HlLtJ, CAST/EiJ, PWK/PhJ, and WSB/EiJ. Hindlimb unloading (HLU) is the best model for simulating local and systemic contributors of disuse and therefore may have a greater impact on bones than immobilization. We hypothesized that genetic variation would affect the response to HLU across the eight founder strains. Mice of each founder strain were placed in HLU for 3 weeks, and the femurs and tibias were analyzed. There were significant HLU and mouse strain interactions on body weight, femur trabecular BV/TV, and femur ultimate force. This indicates that unloading only caused significant catabolic effects in some mouse strains. C57BL/6 J mice were most affected by unloading while other strains were more protected. There were significant HLU and mouse strain interactions on gene expression of genes encoding bone metabolism genes in the tibia. This indicates that unloading only caused significant effects on bone metabolism genes in some mouse strains. Different mouse strains respond to HLU differently, and this can be explained by genetic differences. These results suggest the outbred J:DO mice will be a powerful model for examining the effects of genetics on the skeletal response to HLU.