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GLP-1 promotes osteogenic differentiation of human ADSCs via the Wnt/GSK-3β/β-catenin pathway.
Mol Cell Endocrinol. 2020 Jun 29 [Online ahead of print]MC

Abstract

Glucagon-like peptide-1 (GLP-1) analogues are promising anti-diabetic drugs which had been shown to have beneficial effects on bone metabolism in clinical practice, but the molecular mechanism remains unclear. In this study, we evaluated whether GLP-1 can affect the "intestine-fat-bone axis" via the Wnt/GSK-3β/β-catenin pathway. We established a diabetic mouse model and then treated mice with GLP-1 analogue liraglutide. The results showed that after liraglutide treatment, glucose tolerance and insulin tolerance were significantly improved in diabetic mice as expected. Moreover, osteogenic markers such as collagenⅠ, Runx2 and OCN were upregulated; and the adipogenic differentiation markers C/EBP-α and PPAR-γ were downregulated, these results indicated that liraglutide could ameliorate the osteogenic metabolism in diabetic mice. In the cell model, human ADSCs (hADSCs) were cultured and induced to undergo osteogenic and adipogenic differentiation under high glucose conditions in vitro and then treated with GLP-1. The results showed that GLP-1 repressed the induction of adipocyte differentiation biomarkers and the secretion of GSK-3β in a dose-dependent manner. In addition, GLP-1 enhanced the expression of osteoblastogenic biomarkers, such as OCN, Runx2 and collagenⅠ, and promoted osteoblastic mineralization. These effects were substantially suppressed by the Wnt signal recombinant human DKK-1 or activated by Wnt pathway agonist LiCl. Silencing of GSK-3β showed that the levels of β-catenin, GSK-3β and Runx2 were significantly increased by 2.46-, 2.05-, 4.44-fold after GLP-1 treatment compared to that observed in the GSK-3β lentiviral group, respectively. We conclude that GLP-1 promotes the osteogenic differentiation of hADSCs via the Wnt/GSK-3β/β-catenin pathway.

Authors+Show Affiliations

Department of Endocrinology & Metabolism, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong Province, 519000, China; Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong Province, 519000, China.Department of Endocrinology & Metabolism, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong Province, 519000, China.Department of Endocrinology & Metabolism, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong Province, 519000, China.Department of Endocrinology & Metabolism, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong Province, 519000, China.Department of Endocrinology & Metabolism, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong Province, 519000, China.Department of Endocrinology & Metabolism, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong Province, 519000, China.Department of Endocrinology & Metabolism, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong Province, 519000, China; Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong Province, 519000, China. Electronic address: luhongy@mail.sysu.edu.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32615283

Citation

Li, Yun, et al. "GLP-1 Promotes Osteogenic Differentiation of Human ADSCs Via the Wnt/GSK-3β/β-catenin Pathway." Molecular and Cellular Endocrinology, 2020, p. 110921.
Li Y, Fu H, Wang H, et al. GLP-1 promotes osteogenic differentiation of human ADSCs via the Wnt/GSK-3β/β-catenin pathway. Mol Cell Endocrinol. 2020.
Li, Y., Fu, H., Wang, H., Luo, S., Wang, L., Chen, J., & Lu, H. (2020). GLP-1 promotes osteogenic differentiation of human ADSCs via the Wnt/GSK-3β/β-catenin pathway. Molecular and Cellular Endocrinology, 110921. https://doi.org/10.1016/j.mce.2020.110921
Li Y, et al. GLP-1 Promotes Osteogenic Differentiation of Human ADSCs Via the Wnt/GSK-3β/β-catenin Pathway. Mol Cell Endocrinol. 2020 Jun 29;110921. PubMed PMID: 32615283.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - GLP-1 promotes osteogenic differentiation of human ADSCs via the Wnt/GSK-3β/β-catenin pathway. AU - Li,Yun, AU - Fu,Huirong, AU - Wang,Hou, AU - Luo,Shunkui, AU - Wang,Lingling, AU - Chen,Jiandi, AU - Lu,Hongyun, Y1 - 2020/06/29/ PY - 2020/01/16/received PY - 2020/06/19/revised PY - 2020/06/21/accepted PY - 2020/7/3/entrez PY - 2020/7/3/pubmed PY - 2020/7/3/medline KW - Adipose-derived stem cells (ADSCs) KW - GLP-1 KW - Intestine-fat-bone axis KW - Osteogenic differentiation KW - Wnt/GSK-3β/β-catenin signaling pathway SP - 110921 EP - 110921 JF - Molecular and cellular endocrinology JO - Mol. Cell. Endocrinol. N2 - Glucagon-like peptide-1 (GLP-1) analogues are promising anti-diabetic drugs which had been shown to have beneficial effects on bone metabolism in clinical practice, but the molecular mechanism remains unclear. In this study, we evaluated whether GLP-1 can affect the "intestine-fat-bone axis" via the Wnt/GSK-3β/β-catenin pathway. We established a diabetic mouse model and then treated mice with GLP-1 analogue liraglutide. The results showed that after liraglutide treatment, glucose tolerance and insulin tolerance were significantly improved in diabetic mice as expected. Moreover, osteogenic markers such as collagenⅠ, Runx2 and OCN were upregulated; and the adipogenic differentiation markers C/EBP-α and PPAR-γ were downregulated, these results indicated that liraglutide could ameliorate the osteogenic metabolism in diabetic mice. In the cell model, human ADSCs (hADSCs) were cultured and induced to undergo osteogenic and adipogenic differentiation under high glucose conditions in vitro and then treated with GLP-1. The results showed that GLP-1 repressed the induction of adipocyte differentiation biomarkers and the secretion of GSK-3β in a dose-dependent manner. In addition, GLP-1 enhanced the expression of osteoblastogenic biomarkers, such as OCN, Runx2 and collagenⅠ, and promoted osteoblastic mineralization. These effects were substantially suppressed by the Wnt signal recombinant human DKK-1 or activated by Wnt pathway agonist LiCl. Silencing of GSK-3β showed that the levels of β-catenin, GSK-3β and Runx2 were significantly increased by 2.46-, 2.05-, 4.44-fold after GLP-1 treatment compared to that observed in the GSK-3β lentiviral group, respectively. We conclude that GLP-1 promotes the osteogenic differentiation of hADSCs via the Wnt/GSK-3β/β-catenin pathway. SN - 1872-8057 UR - https://www.unboundmedicine.com/medline/citation/32615283/GLP-1_promotes_osteogenic_differentiation_of_human_ADSCs_via_the_Wnt/GSK-3β/β-catenin_pathway L2 - https://linkinghub.elsevier.com/retrieve/pii/S0303-7207(20)30221-5 DB - PRIME DP - Unbound Medicine ER -
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