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| Status |
Public on May 10, 2010 |
| Title |
Differential gene expression profiles of long bones of telomerase deficient mice (G3-mTERC-/-) |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Telomere shortening due to telomerase deficiency leads to accelerated senescence of human skeletal (mesenchymal) stem cells (MSC) in vitro. In order to study the role of telomere shortening in vivo, we studied the phenotype of telomerase deficient mice caused by absence of telomerase RNA component (TERC-/-). TERC-/- exhibited accelerated age-related bone loss starting at 3 months of age and during 12 months follow up. Bone histomorphometry revealed decreased mineralized surface and bone formation rate as well as increased osteoclast number and size in TERC-/-. Also, serum total deoxy-pyridinoline (tDPD) was increased in TERC-/-. MSC isolated from TERC-/- exhibited intrinsic defects with reduced total number, lower proliferation rate, decreased expression of osteoblastic (OB) differentiation markers and formed less in vivo ectopic bone compared to WT cells. The TERC-/--MSC cultures accumulated a larger proportion of senescent ß-galactosidase+ cells and cells exhibiting DNA damage positive for γ-H2AX. Micro-array analysis of bones of TERC-/- and WT revealed significant over-expression of a large number of pro-inflammatory genes and signaling pathways in TERC-/- known to control osteoclast (OC) differentiation. In accordance with that, serum from TERC-/- enhanced OC formation in control bone marrow cultures. Our data demonstrate two mechanisms for age-related bone loss caused by telomerase deficiency: intrinsic osteoblastic defects and creation of pro-inflammatory osteoclast-activating microenvironment. Approaches for re-telomerization of MSC may provide a novel approach for abolishing age-related bone loss.
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| Overall design |
control (WT) and the test (G3 - mTERC-/-) samples
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| Contributor(s) |
Saeed H, Abdallah BM, Kassem M |
| Citation(s) |
21308778 |
| Submission date |
Apr 26, 2010 |
| Last update date |
Jan 16, 2019 |
| Contact name |
Hamid Saeed |
| E-mail(s) |
hsaeed@health.sdu.dk
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| Phone |
+45 3141 7861
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| Fax |
+45 6550 3950
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| URL |
http://www.mbc.sdu.dk
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| Organization name |
Odense University Hospital/ University of Southern Denmark
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| Department |
Endocrinology
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| Lab |
KMEB Lab
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| Street address |
Winslows parken 1st floor
|
| City |
odense |
| State/province |
Fyn |
| ZIP/Postal code |
5000 C |
| Country |
Denmark |
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| Platforms (1) |
| GPL6887 |
Illumina MouseWG-6 v2.0 expression beadchip |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA125957 |
