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| Status |
Public on Sep 30, 2024 |
| Title |
Girk3 deletion increases osteoblast maturation and bone mass accrual in adult male mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Osteoporosis and other metabolic bone diseases are prevalent in the aging population. While bone has the capacity to regenerate throughout life, bone formation rates decline with age and contribute to reduced bone density and strength. Identifying mechanisms and pathways that increase bone accrual in adults could prevent fractures and accelerate healing. G protein-gated inwardly rectifying K+ (GIRK) channels are key effectors of G protein-coupled receptor signaling. Girk3 was recently shown to regulate endochondral ossification. Here, we demonstrate that deletion of Girk3 increases bone mass after 18 weeks of age. Male 24-week-old Girk3-/- mice have greater trabecular bone mineral density and bone volume fraction than WT mice. Osteoblast activity is moderately increased in 24-week-old Girk3-/- mice compared to WT mice. In vitro, both calvarial osteoblasts and bone marrow stromal cells from Girk3-/- mice are more osteogenic than WT cells and have altered expression of genes that regulate the wingless-type MMTV integration site (Wnt) family. Wnt inhibition via Dickkopf-1 (Dkk1) or β-catenin inhibition via XAV939 prevents the enhanced mineralization, but not proliferation, in Girk3-/- BMSCs and slows these processes in WT cells. Finally, selective ablation of Girk3 from cells expressing Cre from the 2.3kb-Col1a1 promoter, including osteoblasts and osteocytes, is sufficient to increase bone mass and bone strength in male mice at 24 weeks of age. Taken together, these data demonstrate that Girk3 regulates progenitor cell proliferation, osteoblast differentiation, and bone mass accrual in adult male mice.
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| Overall design |
Femurs were isolated from 24 week old WT (n=4) and Girk3-/- (n=4) male mice. The diaphyses were cut off, marrow was flushed, and the bones were flushed with PBS to isolate diaphyseal bone. Bone was homogenized in Trizol, then total RNA was extracted and sent for bulk RNA Sequencing.
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| Contributor(s) |
Weaver S, Westendorf J |
| Citation(s) |
39228688 |
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| Submission date |
Apr 17, 2024 |
| Last update date |
Sep 30, 2024 |
| Contact name |
Alexandra Krivonos |
| Organization name |
Mayo Clinic
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| Department |
Quantitative Health Sciences
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| Street address |
200 1st St SW
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| City |
Rochester |
| State/province |
MN |
| ZIP/Postal code |
55905 |
| Country |
USA |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA1101450 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE264200_raw_counts.csv.gz |
540.5 Kb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
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