Impaired Bone Fracture Healing in Type 2 Diabetes Is Caused by Defective Functions of Skeletal Progenitor Cells

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

Impaired Bone Fracture Healing in Type 2 Diabetes Is Caused by Defective Functions of Skeletal Progenitor Cells

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Impaired Bone Fracture Healing in Type 2 Diabetes Is Caused by Defective Functions of Skeletal Progenitor Cells

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10601 - Cell biology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Stem Cells

ISSN

1066-5099

e-ISSN

1549-4918

Svazek periodika

40

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

16

Strana od-do

149-164

Kód UT WoS článku

000768399300001

EID výsledku v databázi Scopus

2-s2.0-85126830303