Aims

Our objective was to study the vascular smooth muscle cells (VSMC) osteoblastic transdifferentiation in AGE exposed cells or those from diabetic animals, and its response to metformin treatment.

Methods

VSMC were obtained from non-diabetic rats, grown with or without AGE; while VSMC of in vivo-ex vivo studies were obtained from non-diabetic control animals (C), diabetic (D), C treated with metformin (M) and D treated with metformin (D-M). We studied the osteoblastic differentiation by evaluating alkaline phosphatase (ALP), type I collagen (Col) and mineral deposit.

Results

In vitro, AGE increased proliferation, migration, and osteoblastic differentiation of VSMC. Metformin cotreatment prevented the AGE induced proliferation and migration. Both AGE and metformin stimulated the expression of ALP and Col. AGE induced mineralization was prevented by metformin. VSMC from D expressed a higher production of Col and ALP. Those from D-M showed an ALP increase vs C and M, and a partial decrease vs D. Cultured in osteogenic medium, ALP, Col and mineralization increased in D vs C, remained unchanged in M, and were prevented in D-M animals.

Conclusion

Both AGE and DM favor VSMC differentiation towards the osteogenic phenotype and this effect can be prevented by metformin.

中文翻译：

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晚期糖基化终末产物、糖尿病和二甲双胍对血管平滑肌细胞成骨细胞转分化能力的影响：体内和体外研究

目标

我们的目的是研究AGE暴露细胞或糖尿病动物细胞中血管平滑肌细胞 (VSMC) 成骨细胞转分化及其对二甲双胍治疗的反应。

方法

VSMC 取自非糖尿病大鼠，在有或没有 AGE 的情况下生长；而体内-离体研究的 VSMC 是从非糖尿病对照动物 (C)、糖尿病对照动物 (D)、用二甲双胍治疗的 C (M) 和用二甲双胍治疗的 D (DM) 获得的。我们通过评估碱性磷酸酶 (ALP)、 I 型胶原蛋白 (Col) 和矿物质沉积来研究成骨细胞分化。

结果

在体外，AGE 增加 VSMC 的增殖、迁移和成骨细胞分化。二甲双胍联合治疗可防止 AGE 诱导的增殖和迁移。AGE 和二甲双胍均刺激 ALP 和 Col 的表达。二甲双胍可阻止 AGE 诱导的矿化。来自 D 的 VSMC 表达了更高的 Col 和 ALP 产量。与 C 和 M 相比，DM 动物的 ALP 增加，与 D 相比部分减少。在成骨培养基中培养，D 中的 ALP、Col 和矿化作用比 C 中增加，M 中保持不变，而在 DM 动物中则被阻止。

结论

AGE 和 DM 都有利于 VSMC 向成骨表型分化，二甲双胍可以预防这种效应。