Metformin hydrochloride antagonizes glucotoxicity in osteoblasts by restraining the expression of PPARγ
- Author:
Sun-Jie YAN
1
Author Information
- Publication Type:Journal Article
- Keywords: Bone morphogenetic protein-2; Metformin hydrochloride; Osteoblasts; Peroxisome proliferator-activated receptor γ
- From: Chinese Pharmaceutical Journal 2014;49(2):121-125
- CountryChina
- Language:Chinese
- Abstract: OBJECTIVE: To investigate the protective effects of metformin hydrochloride (MF) on osteoblasts which were exposed to constant high glucose condition, and the relationship between MF and the expression of peroxisome proliferator-activated receptor (PPAR)γ. METHODS: Mouse cranium osteoblasts were cultured in vitro and divided into 5.5 mmol · L-1 normal glucose +0 μmol · L-1 MF group, 25 mmol · L-1 high glucose with different concentration of MF (0, 25, 50, 100 μmol · L-1 MF, respectively) and intervened for 1,2 and 3 w, then the mRNA expression levels of PPARγ and bone morphogenetic protein (BMP)-2 were detected by RT-PCR, and the protein expression levels of PPARγ was examined by Western blot. RESULTS (1)The mRNA expression levels of PPARγ was marked higher in high glucose group compared to the control group with the same intervene time (all P < 0.05); when the intervention time prolonged to 3w, the protein expression of PPARγ increased significantly (P < 0.05); the mRNA expression levels of BMP-2 in the high glucose group was lower than in the control group (all P < 0.05). (2)At the same intervening time, the expression of PPARγ mRNA decreased while BMP-2 mRNA increased (all P < 0.05) with the increasing concentration of MF (from 0 μmol · L-1 to 100 μmol · L-1); when the intervention time prolonged from 1w to 3w, the mRNA expression levels of PPARγ increased in all the high glucose groups while the mRNA expression levels of BMP-2 decreased (all P < 0.05). (3)When interviewed for 3w, the protein expression of PPARγ decreased gradually with the increasing concentration of MF in high glucose condition (P < 0.05). CONCLUSION: Pathological concentration of glucose could lead to poorly differentiated of osteoblasts, which might association with the enhanced mRNA and protein expression levels of PPARγ; MF can protect osteoblasts by restraining the expression of PPARγ.
