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| Status |
Public on Jul 10, 2024 |
| Title |
Differential but complementary roles of HIF-1α and HIF-2α in the regulation of bone homeostasis |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Bone is a highly dynamic tissue undergoing continuous formation and resorption. Here, we investigated differential but complementary roles of hypoxia-inducible factor (HIF)-1α and HIF-2α in regulating bone remodeling. Using RNA-seq analysis, we identified that specific genes involved in regulating osteoblast differentiation were similarly but slightly differently governed by HIF-1α and HIF-2α. We found that increased HIF-1α expression inhibited osteoblast differentiation via inhibiting RUNX2 function by upregulation of Twist2, confirmed using Hif1a conditional knockout (KO) mouse. Ectopic expression of HIF-1α via adenovirus transduction resulted in the increased expression and activity of RANKL, while knockdown of Hif1a expression via siRNA or osteoblast-specific depletion of Hif1a in conditional KO mice had no discernible effect on osteoblast-mediated osteoclast activation. The unexpected outcome was elucidated by the upregulation of HIF-2α upon Hif1a overexpression, providing evidence that Hif2a is a transcriptional target of HIF-1α in regulating RANKL expression, verified through an experiment of HIF-2α knockdown after HIF-1α overexpression. The above results were validated in an ovariectomized- and aging-induced osteoporosis model using Hif1a conditional KO mice. Our findings conclude that HIF-1α plays an important role in regulating bone homeostasis by controlling osteoblast differentiation, and in influencing osteoclast formation through the regulation of RANKL secretion via HIF-2α modulation.
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| Overall design |
RNA-seq analysis was performed to determine the gene expression profile caused by overexpression of HIF-1α and HIF-2α during primary culture calvarial preosteoblast differentiation.
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| Contributor(s) |
Ryu J, Huh Y, Lee S, Kim S |
| Citation(s) |
39039245 |
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| Submission date |
Jul 08, 2024 |
| Last update date |
Aug 16, 2024 |
| Contact name |
Su-Jin Kim |
| E-mail(s) |
ksz1353@naver.com
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| Phone |
+82-62-530-4868
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| Organization name |
Chonnam National University
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| Street address |
77, Yongbong-ro, Buk-gu, Gwangju, Republic of Korea
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| City |
Gwangju |
| ZIP/Postal code |
61186 |
| Country |
South Korea |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (9)
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| GSM8383598 |
osteoblast, ad-Hif1a 1, Day6 |
| GSM8383599 |
osteoblast, ad-Hif1a 2, Day6 |
| GSM8383600 |
osteoblast, ad-Hif1a 3, Day6 |
| GSM8383601 |
osteoblast, ad-Hif2a 1, Day6 |
| GSM8383602 |
osteoblast, ad-Hif2a 2, Day6 |
| GSM8383603 |
osteoblast, ad-Hif2a 3, Day6 |
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| Relations |
| BioProject |
PRJNA1133004 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE271730_RAW.tar |
1.7 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
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