title: The bone-preserving effects of exendin-4 in ovariectomized rats.
abstract: 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.
authors.affiliation: Department of Endocrine and Metabolic Diseases, Rui-jin Hospital, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Jiao-tong University School of Medicine, 197 Rui-jin Er Road, Shanghai, 200025, China.|Shanghai Tongren Hospital, Shanghai Jiao-tong University School of Medicine, Shanghai, China.
authors.forename: Han-Xiao
authors.initials: HX
authors.lastname: Sun
authors.affiliation: Department of Endocrine and Metabolic Diseases, Rui-jin Hospital, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Jiao-tong University School of Medicine, 197 Rui-jin Er Road, Shanghai, 200025, China.|Renji Hospital, Shanghai Jiao-tong University School of Medicine, Shanghai, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Lu
authors.affiliation: Department of Endocrine and Metabolic Diseases, Rui-jin Hospital, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Jiao-tong University School of Medicine, 197 Rui-jin Er Road, Shanghai, 200025, China.
authors.forename: Dong-Mei
authors.initials: DM
authors.lastname: Liu
authors.affiliation: Department of Endocrine and Metabolic Diseases, Rui-jin Hospital, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Jiao-tong University School of Medicine, 197 Rui-jin Er Road, Shanghai, 200025, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Endocrine and Metabolic Diseases, Rui-jin Hospital, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Jiao-tong University School of Medicine, 197 Rui-jin Er Road, Shanghai, 200025, China.
authors.forename: Li-Hao
authors.initials: LH
authors.lastname: Sun
authors.affiliation: Department of Endocrine and Metabolic Diseases, Rui-jin Hospital, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Jiao-tong University School of Medicine, 197 Rui-jin Er Road, Shanghai, 200025, China.
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Zhao
authors.affiliation: Department of Endocrine and Metabolic Diseases, Rui-jin Hospital, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Jiao-tong University School of Medicine, 197 Rui-jin Er Road, Shanghai, 200025, China. liujianmin@medmail.com.cn.
authors.forename: Jian-Min
authors.initials: JM
authors.lastname: Liu
authors.affiliation: Department of Endocrine and Metabolic Diseases, Rui-jin Hospital, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Jiao-tong University School of Medicine, 197 Rui-jin Er Road, Shanghai, 200025, China. catherine-tao@163.com.
authors.forename: Bei
authors.initials: B
authors.lastname: Tao
mesh_terms: D050156:Adipogenesis / Q000187:drug effects*; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D024042:Collagen Type I / Q000378:metabolism; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D000077270:Exenatide; D005260:Female; D005269:Femur / Q000187:drug effects* / Q000378:metabolism; D008159:Lumbar Vertebrae / Q000187:drug effects* / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D010052:Ovariectomy; D047495:PPAR gamma / Q000235:genetics; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014688:Venoms / Q000494:pharmacology*
chemical_list: D024042:Collagen Type I; D050659:Core Binding Factor Alpha 1 Subunit; D047495:PPAR gamma; D010455:Peptides; D014688:Venoms; D000077270:Exenatide; D000469:Alkaline Phosphatase
keywords: Bone micro-architecture; Bone mineral density; Exendin-4; Ovariectomy; Rat