J Menopausal Med. 2015 Aug;21(2):93-103. doi: 10.6118/jmm.2015.21.2.93. Epub 2015 Aug 28.
Effect of Glucagon-like Peptide-1 on the Differentiation of Adipose-derived Stem Cells into Osteoblasts and Adipocytes.
Journal of menopausal medicine
Hye Min Lee, Bo Sun Joo, Chang Hoon Lee, Heung Yeol Kim, Ji Hoon Ock, Young Seok Lee
Affiliations
Affiliations
- Department of Molecular Biology, Natural Science College, Pusan National University, Busan, Korea.
- Research Center for Anti-Aging Technology Development, Pusan National University, Busan, Korea.
- Department of Obstetrics and Gynecology, Kosin University Hospital, Busan, Korea.
- Department of Obstetrics and Gynecology, Busan Adventist Hospital, Busan, Korea.
- Department of Pediatric Cardiology, Dona-A University Hospital, Busan, Korea.
PMID: 26357647
PMCID: PMC4561747 DOI: 10.6118/jmm.2015.21.2.93
Abstract
OBJECTIVES: Glucagon-like peptide-1 (GLP-1) is an intestinally secreted hormone and it plays an important role in the regulation of glucose homeostasis. However, the possible role of GLP-1 in the differentiation of adipose-derived stem cells (ADSCs) remains unknown. Therefore this study investigated the effect of GLP-1 on the differentiation of ADSCs into osteoblasts and adipocytes.
METHODS: ADSCs were isolated from human adipose tissues of the abdomens, cultured and characterized by flow cytometry and multi-lineage potential assay. ADSCs were induced in osteogenic and adipogenic media treated with two different doses (10 and 100 nM) of GLP-1, and then the effect of GLP-1 on differentiation of ADSCs into osteoblast and adipocyte was examined. The signaling pathway involved in these processes was also examined.
RESULTS: Isolated human ADSCs expressed mesenchymal stem cell (MSC) specific markers as well as GLP-1 receptor (GLP-1R) proteins. They also showed multiple-lineage potential of MSC. GLP-1 was upregulated the activity and mRNA expression of osteoblast-specific marker, alkaline phosphatase and the mineralization of calcium. In contrast, GLP-1 significantly suppressed the expression of adipocyte-specific markers, peroxisome proliferator-activated receptor gamma (PPAR-γ), lipoprotein lipase (LPL) and adipocyte protein 2 (AP2). This decreased expression of adipocyte specific markers caused by GLP-1 was significantly reversed by the treatment of extracellular signal-regulated kinase (ERK) inhibitor, PD98059 (P < 0.05).
CONCLUSION: This result demonstrates that GLP-1 stimulates osteoblast differentiation in ADSCs, whereas it inhibits adipocyte differentiation. The ERK signaling pathway seems to be involved in these differentiation processes mediated by GLP-1.
Keywords: Adipocytes; Adipogenesis; Adipose tissue; Cell differentiation; Glucagon-like peptide 1; Osteogenesis
References
- J Clin Endocrinol Metab. 2001 Aug;86(8):3853-60 - PubMed
- Mol Biol Cell. 2002 Dec;13(12):4279-95 - PubMed
- J Biol Chem. 2010 Jan 15;285(3):1989-2002 - PubMed
- Int J Mol Med. 2013 Jun;31(6):1429-35 - PubMed
- JAMA Intern Med. 2013 Apr 8;173(7):534-9 - PubMed
- Calcif Tissue Int. 2009 Jun;84(6):453-61 - PubMed
- Cell Cycle. 2006 Jan;5(2):176-9 - PubMed
- J Cell Physiol. 2010 Nov;225(2):585-92 - PubMed
- Exp Clin Endocrinol Diabetes. 2001;109 Suppl 2:S288-303 - PubMed
- Am J Physiol Endocrinol Metab. 2010 Mar;298(3):E634-43 - PubMed
- BMC Physiol. 2011 Jul 29;11:12 - PubMed
- Biogerontology. 2001;2(3):165-71 - PubMed
- Curr Opin Rheumatol. 2008 Jul;20(4):429-34 - PubMed
- J Neurochem. 2005 Feb;92(4):798-806 - PubMed
- J Neurochem. 1996 Mar;66(3):920-7 - PubMed
- Clin Orthop Relat Res. 1971 Oct;80:147-54 - PubMed
- Endocrinology. 2008 Feb;149(2):574-9 - PubMed
- J Endocrinol. 2011 May;209(2):203-10 - PubMed
- Physiol Rev. 2007 Oct;87(4):1409-39 - PubMed
- J Clin Invest. 2004 Mar;113(6):846-55 - PubMed
- PPAR Res. 2008;2008:297893 - PubMed
- Aging Cell. 2004 Dec;3(6):379-89 - PubMed
- Phytother Res. 2009 May;23(5):713-8 - PubMed
- Circulation. 2004 Mar 2;109(8):962-5 - PubMed
- Nat Biotechnol. 2004 May;22(5):560-7 - PubMed
- J Cell Sci. 1992 Jun;102 ( Pt 2):341-51 - PubMed
- N Engl J Med. 1992 May 14;326(20):1316-22 - PubMed
- Bone. 1995 Aug;17(2 Suppl):77S-83S - PubMed
- Diabetes Obes Metab. 2009 Oct;11(10):953-65 - PubMed
- Science. 1999 Apr 2;284(5411):143-7 - PubMed
- J Clin Endocrinol Metab. 2006 Sep;91(9):3349-54 - PubMed
- Int J Clin Pract. 2006 Nov;60(11):1454-70 - PubMed
- Cell. 2004 Mar 5;116(5):639-48 - PubMed
- J Nat Med. 2011 Jul;65(3-4):424-30 - PubMed
- J Biol Chem. 2012 Feb 24;287(9):6421-30 - PubMed
Publication Types