The bone-preserving effects of exendin-4 in ovariectomized rats

• Published in: Endocrine Vol. 51; no. 2; pp. 323 - 332
• Main Authors: Sun, Han-xiao, Lu, Nan, Liu, Dong-mei, Zhao, Lin, Sun, Li-hao, Zhao, Hong-yan, Liu, Jian-min, Tao, Bei
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.02.2016
• Subjects: Adipogenesis - drug effects; Alkaline Phosphatase - metabolism; Animals; Bone Density - drug effects; Collagen Type I - metabolism; Core Binding Factor Alpha 1 Subunit - metabolism; Diabetes; Endocrinology; Female; Femur - drug effects; Femur - metabolism; Humanities and Social Sciences; Internal Medicine; Lumbar Vertebrae - drug effects; Lumbar Vertebrae - metabolism; Medicine; Medicine & Public Health; Mesenchymal Stromal Cells - drug effects; Mesenchymal Stromal Cells - metabolism; multidisciplinary; Original Article; Osteogenesis - drug effects; Ovariectomy; Peptides - pharmacology; PPAR gamma - genetics; Rats; Rats, Wistar; Science; Venoms - pharmacology; Bone mineral density; Bone micro-architecture; Ovariectomy; Rat; Exendin-4
• ISSN: 1355-008X; 1559-0100
• DOI: 10.1007/s12020-015-0667-x

Exendin-4 was found to be beneficial to the skeleton in diabetic rodents. In this study, we assessed the changes of bone mineral densities (BMDs) and quality in non-diabetic ovariectomized (OVX) rats after treatment with exendin-4. The regulatory role of exendin-4 on osteoblastogenesis and adipogenesis in rat bone marrow stromal cells (BMSCs) was also explored. Three months after sham surgery or OVX, 18 5-month-old female Wistar rats were divided into three groups and received the following treatment for 8 weeks: (1) Sham + vehicle; (2) OVX + vehicle; and (3) OVX + exendin-4 20 µg/kg/day. Micro-CT and three-point bending test were used to evaluate the BMDs, bone morphometric parameters, and biomechanical properties. Real-time PCR and Western blot were performed to measure gene and protein expression after exendin-4 treatment in adipogenesis and osteoblastogenesis of rat BMSCs. Exendin-4 could improve trabecular volume, thickness, and number, increase BMD, and reduce trabecular spacing in the lumbar spine and femur of OVX rats. Exendin-4 had little impact on the mechanical resistance of femurs to fracture. When rat BMSCs were treated with exendin-4, the mRNA expression levels of runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP), and collagen α1 (Coll-1) were increased, while those of peroxisome proliferators activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein (C/EBPα) decreased. Exendin-4 treatment also resulted in increased expression levels of p38, p42/44, and β-catenin proteins. Exendin-4 was anabolic to bone in OVX rats possibly by facilitating osteoblastogenesis while repressing adipogenesis during BMSC lineage differentiation.