Abstract
Recently, a number of studies have demonstrated the potential beneficial role for novel anti-diabetic GLP-1 receptor agonists (GLP-1RAs) in the skeleton metabolism in diabetic rodents and patients. In this study, we evaluated the impacts of the synthetic GLP-1RA Liraglutide on bone mass and quality in osteoporotic rats induced by ovariectomy (OVX) but without diabetes, as well as its effect on the adipogenic and osteoblastogenic differentiation of bone marrow stromal cells (BMSCs). Three months after sham surgery or bilateral OVX, eighteen 5-month old female Wistar rats were randomly divided into three groups to receive the following treatments for 2 months: (1) Sham + normal saline; (2) OVX + normal saline; and (3) OVX + Liraglutide (0.6 mg/day). As revealed by micro-CT analysis, Liraglutide improved trabecular volume, thickness and number, increased BMD, and reduced trabecular spacing in the femurs in OVX rats; similar results were observed in the lumbar vertebrae of OVX rats treated with Liraglutide. Following in vitro treatment of rat and human BMSCs with 10 nM Liraglutide, there was a significant increase in the mRNA expression of osteoblast-specific transcriptional factor Runx2 and the osteoblast markers alkaline phosphatase (ALP) and collagen α1 (Col-1), but a significant decrease in peroxisome proliferator-activated receptor γ (PPARγ). In conclusion, our results indicate that the anti-diabetic drug Liraglutide can exert a bone protective effect even in non-diabetic osteoporotic OVX rats. This protective effect is likely attributable to the impact of Liraglutide on the lineage fate determination of BMSCs.
Highlights
Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) are a new class of anti-diabetic medications that mimic the effects of incretin hormones [1]
Liraglutide treatment of OVX rats induced a significant improvement in trabecular thickness by 36% (P = 0.023), trabecular number by 20% (P = 0.039), and trabecular bone mineral densities (BMDs) by 4% (P = 0.001) compared to their OVX littermates treated with vehicle in the fifth lumbar vertebra
Analysis of the right femur using micro-CT displayed an increase in BV/TV by 27% (P = 0.049), cortical thickness by 5% (P = 0.020), cortical BMD by 1% (P = 0.008), trabecular thickness by 11% (P = 0.033), trabecular number by 24% (P = 0.002), and trabecular BMD by 2% (P = 0.015), and a decrease in trabecular spacing by 42% (P = 0.032) in the Liraglutide-treated OVX rats (Fig 2B)
Summary
Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) are a new class of anti-diabetic medications that mimic the effects of incretin hormones [1]. In addition to its glucose-lowering effect, GLP-1 delays gastric emptying and inhibits appetite, possibly by affecting vagal afferent fibers and the hypothalamus, eventually leading to weight loss [3, 4]. These favorable actions of GLP-1 on glucose homeostasis are mediated through GLP-1 receptors. Liraglutide, a synthetic GLP-1RA that share 97% homology with the structure of human GLP-1, is resistant to DPP-IV inactivation and possesses a much longer circulating half-life, thereby making it a novel anti-diabetic drug suitable for once-daily injection[1]
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