Transcriptional changes and preservation of bone mass in hibernating black bears
Abstract 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...
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Nature Portfolio
2021-04-01
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Series: | Scientific Reports |
Online Access: | https://doi.org/10.1038/s41598-021-87785-9 |
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author | Anna V. Goropashnaya Øivind Tøien Thiruvarangan Ramaraj Anitha Sundararajan Faye D. Schilkey Brian M. Barnes Seth W. Donahue Vadim B. Fedorov |
author_facet | Anna V. Goropashnaya Øivind Tøien Thiruvarangan Ramaraj Anitha Sundararajan Faye D. Schilkey Brian M. Barnes Seth W. Donahue Vadim B. Fedorov |
author_sort | Anna V. Goropashnaya |
collection | DOAJ |
description | Abstract 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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institution | Directory Open Access Journal |
issn | 2045-2322 |
language | English |
last_indexed | 2024-12-14T15:50:08Z |
publishDate | 2021-04-01 |
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spelling | doaj.art-bdf5a25c76b3426f9b36eca9db43066e2022-12-21T22:55:23ZengNature PortfolioScientific Reports2045-23222021-04-011111910.1038/s41598-021-87785-9Transcriptional changes and preservation of bone mass in hibernating black bearsAnna V. Goropashnaya0Øivind Tøien1Thiruvarangan Ramaraj2Anitha Sundararajan3Faye D. Schilkey4Brian M. Barnes5Seth W. Donahue6Vadim B. Fedorov7Institute of Arctic Biology, University of Alaska FairbanksInstitute of Arctic Biology, University of Alaska FairbanksSchool of Computing, DePaul UniversityNational Center for Genome ResourcesNational Center for Genome ResourcesInstitute of Arctic Biology, University of Alaska FairbanksDepartment of Biomedical Engineering, University of MassachusettsInstitute of Arctic Biology, University of Alaska FairbanksAbstract 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.https://doi.org/10.1038/s41598-021-87785-9 |
spellingShingle | Anna V. Goropashnaya Øivind Tøien Thiruvarangan Ramaraj Anitha Sundararajan Faye D. Schilkey Brian M. Barnes Seth W. Donahue Vadim B. Fedorov Transcriptional changes and preservation of bone mass in hibernating black bears Scientific Reports |
title | Transcriptional changes and preservation of bone mass in hibernating black bears |
title_full | Transcriptional changes and preservation of bone mass in hibernating black bears |
title_fullStr | Transcriptional changes and preservation of bone mass in hibernating black bears |
title_full_unstemmed | Transcriptional changes and preservation of bone mass in hibernating black bears |
title_short | Transcriptional changes and preservation of bone mass in hibernating black bears |
title_sort | transcriptional changes and preservation of bone mass in hibernating black bears |
url | https://doi.org/10.1038/s41598-021-87785-9 |
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