Impaired Bone Fracture Healing in Type 2 Diabetes Is Caused by Defective Functions of Skeletal Progenitor Cells
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F22%3A00556131" target="_blank" >RIV/67985823:_____/22:00556131 - isvavai.cz</a>
Result on the web
<a href="https://doi.org/10.1093/stmcls/sxab011" target="_blank" >https://doi.org/10.1093/stmcls/sxab011</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1093/stmcls/sxab011" target="_blank" >10.1093/stmcls/sxab011</a>
Alternative languages
Result language
angličtina
Original language name
Impaired Bone Fracture Healing in Type 2 Diabetes Is Caused by Defective Functions of Skeletal Progenitor Cells
Original language description
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 and insulinopenia induced by treatment with streptozotocin, we examined bone healing in a tibia cortical bone defect. A delayed bone healing was observed during hyperinsulinemia as newly formed bone was reduced by28.4 +/- 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 (approximate to 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 to34.9 +/- 6.2% which was inversely correlated with glucose levels (R-2 = 0.48, P < .004) and callus adipose tissue area (R-2 = .3711, P < .01). Finally, to investigate the relevance to human physiology, we observed that sera from obese and T2D subjects had disease state-specific inhibitory effects on osteoblast-related gene signatures in human bone marrow stromal cells which resulted in inhibition of osteoblast and enhanced adipocyte differentiation. 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 hyperglycemia per se and not just insulin levels is detrimental for bone healing.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10601 - Cell biology
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Stem Cells
ISSN
1066-5099
e-ISSN
1549-4918
Volume of the periodical
40
Issue of the periodical within the volume
2
Country of publishing house
US - UNITED STATES
Number of pages
16
Pages from-to
149-164
UT code for WoS article
000768399300001
EID of the result in the Scopus database
2-s2.0-85126830303