Blockade of receptors of advanced glycation end products ameliorates diabetic osteogenesis of adipose-derived stem cells through DNA methylation and Wnt signalling pathway

被引：42

作者：

Zhang, Maorui ^{[1
,2
,3
]}

Li, Yong ^{[1
,2
,3
]}

Rao, Pengcheng ^{[3
]}

Huang, Kui ^{[3
]}

Luo, Daowen ^{[3
]}

Cai, Xiaoxiao ^{[2
]}

Xiao, Jingang ^{[1
,3
,4
]}

机构：

[1] Southwest Med Univ, Dept Oral Implantol, Affiliated Stomatol Hosp, Luzhou, Peoples R China

[2] Sichuan Univ, State Key Lab Oral Dis, West China Hosp Stomatol, Chengdu, Sichuan, Peoples R China

[3] Southwest Med Univ, Orofacial Reconstruct & Regenerat Lab, Affiliated Stomatol Hosp, Luzhou, Peoples R China

[4] Southwest Med Univ, Dept Oral & Maxillofacial Surg, Affiliated Stomatol Hosp, Luzhou, Peoples R China

来源：

CELL PROLIFERATION | 2018年 / 51卷 / 05期

基金：

中国国家自然科学基金;

关键词：

EPIGENETIC MODIFICATIONS; DIFFERENTIATION; MELLITUS; FRACTURE; TYPE-1; TISSUE; RAGE;

D O I：

10.1111/cpr.12471

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

ObjectivesDiabetes mellitus-related osteoporosis is caused by the imbalance between bone absorption and bone formation. Advanced glycation end products (AGEs) are considered a cause of diabetic osteoporosis. Although adipose-derived stem cells (ASCs) are promising adult stem cells in bone tissue regeneration, the ability of osteogenesis of ASCs in diabetic environment needs to explore. This study aimed to investigate the influence of AGEs on the osteogenic potential of ASCs and to explore the signalling pathways involved in its effect. Materials and methodsASCs were isolated from inguinal fat and cultured in osteogenic media with or without AGEs and FPS-ZM1, an inhibitor of receptor for AGEs (RAGE). Alizarin red-S, Oil Red-O and Alcian blue staining were used to confirm osteogenic, adipogenic and chondrogenic potential of ASCs, respectively. Immunofluorescence, western blotting and real-time PCR were used to measure changes in markers of osteogenic differentiation, DNA methylation and Wnt signalling. ResultsThe multipotentiality of ASCs was confirmed. Treated with AGEs, OPN and RUNX2 expressions of ASCs were reduced and there was a noticeable loss of mineralization, concomitant with an increase in the expression of RAGE, 5-MC, DNMT1 and DNMT3a. AGEs treatment also led to a loss of Wnt signalling pathway markers, including -Catenin and LEF1, with an increase in GSK-3. Treatment with the RAGE inhibitor, FPS-ZM1, rescued AGEs-induced loss of osteogenic potential, modulated DNA methylation and upregulated Wnt signalling in ASCs. ConclusionsOur results demonstrate that AGEs-RAGE signalling inhibits the osteogenic potential of ASCs under osteoinductive conditions by modulating DNA methylation and Wnt signalling. FPS-ZM1 can rescue the negative effects of AGEs and provide a possible treatment for bone tissue regeneration in patients with diabetic osteoporosis.

引用

页数：11