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| Status |
Public on Oct 01, 2021 |
| Title |
Impaired bone fracture healing in type 2 diabetes is caused by defective functions of skeletal progenitor cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
The mechanisms of obesity and type 2 diabetes (T2D)-associated impaired fracture healing are poorly studied. In a murine model of T2D reflecting both hyperinsulinemia induced by high fat diet (HFD) and insulinopenia induced by treatment with streptozotocin (STZ), we examined bone healing in a tibia cortical bone defect. A delayed bone healing was observed during hyperinsulinemia as newly formed bone was reduced by – 28.4±7.7% and was associated with accumulation of marrow adipocytes at the defect site +124.06±38.71%, and increased density of SCA1+ (+74.99± 29.19%) but not Runx2+osteoprogenitor cells. We also observed increased in reactive oxygen species production (+101.82± 33.05%), senescence gene signature (≈106.66± 34.03%) and LAMIN B1- senescent cell density (+225.18± 43.15%), suggesting accelerated senescence phenotype. During insulinopenia, a more pronounced delayed bone healing was observed with decreased newly formed bone to -34.9± 6.2% which was inversely correlated with glucose levels (R2=0.48, p<0.004) and callus adipose tissue area (R2=0.3711, p<0.01). Finally, to investigate the relevance to human physiology, we observed that sera from obese and T2D patients exerted inhibitory effects on osteoblastic and enhanced adipocyte differentiation of human bone marrow stromal stem cells. Our data demonstrate that T2D exerts negative effects on bone healing through inhibition of osteoblast differentiation of skeletal stem cells and induction of accelerated bone senescence and that the hyperglycaemia per se and not just insulin levels is detrimental for bone healing.
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| Overall design |
mRNA profiles of primary bone marrow derived stromal cells that were differentiated to osteoblasts in vitro in the presence of serum from lean, obese or typ 2 diabtes subjects.
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| Web link |
https://academic.oup.com/stmcls/article/40/2/149/6511690
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| Contributor(s) |
Figeac F, Tencerova M, Ali D, Andersen TL, Appadoo DR, Kerckhofs G, Ditzel N, Kowal JM, Rauch A, Kassem M |
| Citation(s) |
35257177 |
| |
| Submission date |
Jul 20, 2021 |
| Last update date |
Sep 20, 2022 |
| Contact name |
Alexander Rauch |
| E-mail(s) |
arauch@health.sdu.dk
|
| Organization name |
University of Southern Denmark and Odense University Hospital
|
| Department |
Department of Clinical Research
|
| Lab |
Molecular Endocrinology and Stem Cell Research Unit
|
| Street address |
Campusvej 55
|
| City |
Odense |
| ZIP/Postal code |
5230 |
| Country |
Denmark |
| |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (6)
|
| GSM5464032 |
RNA primary BM-MSC serum obese rep 2 |
| GSM5464033 |
RNA primary BM-MSC serum type 2 diabetes rep 1 |
| GSM5464034 |
RNA primary BM-MSC serum type 2 diabetes rep 2 |
|
| Relations |
| BioProject |
PRJNA748427 |
| SRA |
SRP329158 |
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