Expression of Glucagon-Like Peptide 1 Receptor during Osteogenic Differentiation of Adipose-Derived Stem Cells

Abstract

BackgroundGlucagon-like peptide 1 (GLP-1), an incretin hormone well known for its glucose-lowering effect, was recently reported to exert an anabolic effect on bone. Although the exact mechanism is not known, it likely involves the GLP-1 receptor (GLP-1R), which is expressed in some osteoblastic cell lines. Adipose-derived stem cells (ADSCs) have mesenchymal stem cell-specific characteristics, including osteoblastic differentiation potential. We evaluated the expression of GLP-1R during osteogenic differentiation of ADSCs.MethodsADSCs were isolated from subcutaneous adipose tissue obtained from three male donors during plastic surgery and were subjected to osteogenic induction. Mineralization was assessed by Alizarin Red staining on day 21. Expression of alkaline phosphatase (ALP), osteocalcin (OC), and GLP-1R was measured by real-time polymerase chain reaction in triplicate for each patient on days 0, 7, 14, and 21. Target mRNA expression levels were normalized to that of β-actin.ResultsADSCs were fibroblast-like in morphology, adhered to plastic, and had multipotent differentiation potential, as assessed using specific antigen markers. The osteogenic markers ALP and OC were notably upregulated at 21 days. Osteogenic differentiation resulted in a time-dependent increase in the expression of GLP-1R (P=0.013).ConclusionWe demonstrated upregulation of GLP-1R gene expression during osteogenic differentiation of ADSCs. This finding suggests that GLP-1 may induce osteogenic differentiation in bone tissue.

Chronic administration of Glucagon-like peptide-1 receptor agonists improves trabecular bone mass and architecture in ovariectomised mice

“…The presence of pancreatic GLP-1R has also been reported in osteocytic MLO-Y4 cells and osteocytes in rat femurs (35), as well as in mesenchymal stem cells (41). GLP-1R expression is increased during osteogenic differentiation of adipose derived stem cells (ADSCs), suggesting that GLP-1R activation may contribute to osteogenesis (42).…”

Effects of gastric inhibitory polypeptide, glucagon‐like peptide‐1 and glucagon‐like peptide‐1 receptor agonists on Bone Cell Metabolism

“…GIPR indicated but not confirmed GIP protected osteoblast-like cells from apoptosis in a dose-dependent manner Sanz [21] Human mesenchymal stem cells GLP-1 (10 nM) GLP-1R expressed in human mesenchymal stem cells GLP-1 promoted differentiation and decreased apoptosis of human mesenchymal stem cells GLP-1 inhibited adipocyte differentiation, partly through decreasing PPARc Jeon [22] Human adipose-derived stem cells GLP-1R expressed in human adipose-derived stem cells Lee [23] Human adipose-derived stem cells GLP-1 (10 and 100 nM) GLP-1 treatment increased alkaline phosphatase expression (at 100 nM GLP-1). GLP-1 decreased adipogenic differentiation of human adipose-derived stem cells (at 100 nM).…”

“…GLP-1R expression has been reported in human osteoblastic cell lines but may depend on level of osteoblast development as the GLP-1R was expressed in all except the most developed human cell lines (MG63 and TE-85 but not Saos-2) [11]. GLP-1Rs were expressed in human bone marrow stem cells and adipose-derived stem cells retrieved from subcutaneous fat tissue [21,22]. Additionally, GLP-1R expression was augmented during in vitro osteoblastic differentiation of adipose-derived stem cells [22].…”

Mechanisms for the cardiovascular effects of glucagon-like peptide-1

“…GLP-1R is not expressed in thyroid, liver, skeletal muscle and adipose tissue (Wei andMojsov, 1995, Waser et al 2015). It is noteworthy that the number of human tissue-derived cells express GLP-1R, including differentiated human muscle satellite cells (myocytes), umbilical vein endothelial cells, adipose-derived stem cells during osteogenic differentiation and neuroprogenitor cell-derived neurones but not astrocytes or oligodendrocytes (Ding and Zhang, 2012, Green et al 2012, Velmurugan et al 2012, Jeon et al 2014.…”