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Published on: April 7, 2023
Glucagon-like peptide-1 receptor agonist Liraglutide has anabolic bone effects in ovariectomized rats without
Nan Lu1, Hanxiao Sun1, JingJia Yu1
1Department of Endocrine and Metabolic Diseases, Rui-jin Hospital, Shanghai Jiao-tong University School of Medicine, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai 200025, China.
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.
Insights
The anti-diabetic drug Liraglutide improved bone mass and quality in ovariectomized (OVX) rats without diabetes. Liraglutide also promoted osteoblast differentiation in bone marrow stromal cells (BMSCs), suggesting a bone-protective effect.
Area of Science:
- Endocrinology
- Bone Metabolism
- Pharmacology
Background:
- Glucagon-like peptide-1 receptor agonists (GLP-1RAs) show potential benefits for bone metabolism in diabetic conditions.
- The skeletal effects of GLP-1RAs in non-diabetic osteoporotic models require further investigation.
Purpose of the Study:
- To evaluate the impact of the synthetic GLP-1RA, Liraglutide, on bone mass and quality in non-diabetic osteoporotic rats.
- To assess Liraglutide's effect on the differentiation of bone marrow stromal cells (BMSCs) towards osteoblast or adipocyte lineages.
Main Methods:
- Ovariectomy (OVX) was performed on 5-month-old female Wistar rats to induce osteoporosis.
- OVX rats were treated with Liraglutide (0.6 mg/day) or normal saline for 2 months.
- Micro-computed tomography (micro-CT) analyzed bone mass and structure; in vitro studies assessed BMSC differentiation markers.
Main Results:
- Liraglutide treatment significantly improved trabecular bone parameters (volume, thickness, number) and bone mineral density (BMD) in OVX rat femurs and lumbar vertebrae.
- In vitro, Liraglutide increased mRNA expression of osteoblast markers (Runx2, ALP, Col-1) and decreased adipogenic marker (PPARγ) in rat and human BMSCs.
Conclusions:
- Liraglutide demonstrates a bone-protective effect in non-diabetic osteoporotic rats, independent of its anti-diabetic action.
- Liraglutide influences the lineage fate of BMSCs, favoring osteoblastogenesis over adipogenesis, which likely underlies its skeletal benefits.
