Transcriptional changes and preservation of bone mass in hibernating black bears.
Transcriptional changes and preservation of bone mass in hibernating black bears.
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DOI：
10.1038/s41598-021-87785-9
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发表时间：
2021-04-15
影响因子：
4.6
通讯作者：
Fedorov VB
中科院分区：
文献类型：
--
作者：
Goropashnaya AV;Tøien Ø;Ramaraj T;Sundararajan A;Schilkey FD;Barnes BM;Donahue SW;Fedorov VB
在大多数哺乳动物中，缺乏运动会导致骨量和力量的丧失。相比之下，冬眠的熊在冬季长时间(4-6个月)的不动中没有表现出骨丢失，这表明它们有保持骨量的适应机制。为了确定防止废用性骨质疏松症的分子机制的转录变化，我们在小梁骨和骨髓中进行了大规模的基因表达筛选，通过对转录组的测序比较了冬眠和夏季活动的熊。基因集浓缩分析显示，冬眠期间涉及骨吸收、破骨细胞分化和信号转导以及细胞凋亡的基因协同下调。这些发现与以前的组织学发现一致，并可能有助于在冬眠不动期间保存骨骼。相比之下，在冬眠熊骨形成和成骨细胞信号的基因组中没有检测到明显的丰富，表明基因表达的方向性变化。此外，我们还发现了与有氧能量产生有关的基因集的显著和协调的转录诱导，包括脂肪酸β氧化、三羧酸循环、氧化磷酸化和线粒体代谢。线粒体氧化可能受转录诱导的线粒体功能上游刺激物AMPK/Pgc1α途径的上调。
Physical inactivity leads to losses of bone mass and strength in most mammalian species. In contrast, hibernating bears show no bone loss over the prolonged periods (4–6 months) of immobility during winter, which suggests that they have adaptive mechanisms to preserve bone mass. To identify transcriptional changes that underlie molecular mechanisms preventing disuse osteoporosis, we conducted a large-scale gene expression screening in the trabecular bone and bone marrow, comparing hibernating and summer active bears through sequencing of the transcriptome. Gene set enrichment analysis showed a coordinated down-regulation of genes involved in bone resorption, osteoclast differentiation and signaling, and apoptosis during hibernation. These findings are consistent with previous histological findings and likely contribute to the preservation of bone during the immobility of hibernation. In contrast, no significant enrichment indicating directional changes in gene expression was detected in the gene sets of bone formation and osteoblast signaling in hibernating bears. Additionally, we revealed significant and coordinated transcriptional induction of gene sets involved in aerobic energy production including fatty acid beta oxidation, tricarboxylic acid cycle, oxidative phosphorylation, and mitochondrial metabolism. Mitochondrial oxidation was likely up-regulated by transcriptionally induced AMPK/PGC1α pathway, an upstream stimulator of mitochondrial function.
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影响因子：
2.8
作者：
Donahue, SW;Galley, SA;McGee, ME
通讯作者：
McGee, ME
影响因子：
2.4
作者：
Harvey, KB;Donahue, SW
通讯作者：
Donahue, SW
影响因子：
5.9
作者：
Janseng, Heiko T.;Trojahn, Shawn;Kelley, Joanna L.
通讯作者：
Kelley, Joanna L.
通过合成代谢基因的表达升高，在冬眠的黑熊（URSUS Americanus）中保存骨骼质量和结构。
影响因子：
2.9
作者：
Fedorov, Vadim B.;Goropashnaya, Anna V.;Toien, Oivind;Stewart, Nathan C.;Chang, Celia;Wang, Haifang;Yan, Jun;Showe, Louise C.;Showe, Michael K.;Donahue, Seth W.;Barnes, Brian M.
通讯作者：
Barnes, Brian M.
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y