Metformin suppresses Oxidative Stress induced by High Glucose via Activation of the Nrf2/HO-1 Signaling Pathway in Type 2 Diabetic Osteoporosis.
Life Sci
; 312: 121092, 2023 Jan 01.
Article
em En
| MEDLINE
| ID: mdl-36279968
ABSTRACT
BACKGROUND:
Metformin (MET) is widely used as a first-line hypoglycemic agent for the treatment of type 2 diabetes mellitus (T2DM) and was also confirmed to have a therapeutic effect on type 2 diabetic osteoporosis (T2DOP). However, the potential mechanisms of MET in the treatment of T2DOP are unclear.OBJECTIVE:
To clarify the effect of MET in T2DOP and to explore the potential mechanism of MET in the treatment of T2DOP.METHODS:
In vitro, we used MC3T3-E1 cells to study the effects of MET on osteogenic differentiation and anti-oxidative stress injury in a high glucose (Glucose 25 mM) environment. In vivo, we directly used db/db mice as a T2DOP model and assessed the osteoprotective effects of MET by Micro CT and histological analysis.RESULTS:
In vitro, we found that MET increased ALP activity in MC3T3-E1 cells in a high-glucose environment, promoted the formation of bone mineralized nodules, and upregulated the expression of the osteogenesis-related transcription factors RUNX2, Osterix, and COL1A1-related genes. In addition, MET was able to reduce high glucose-induced reactive oxygen species (ROS) production. In studies on the underlying mechanisms, we found that MET activated the Nrf2/HO-1 signaling pathway and alleviated high-glucose-induced oxidative stress injury. In vivo results showed that MET reduced bone loss and bone microarchitecture destruction in db/db mice.CONCLUSION:
Our results suggest that MET can activate the Nrf2/HO-1 signaling pathway to regulate the inhibition of osteogenic differentiation induced by high glucose thereby protecting T2DOP.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Osteoporose
/
Diabetes Mellitus Tipo 2
/
Metformina
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Life Sci
Ano de publicação:
2023
Tipo de documento:
Article