title: Exendin-4, a glucagon-like peptide-1 receptor agonist, prevents osteopenia by promoting bone formation and suppressing bone resorption in aged ovariectomized rats.
abstract: Osteoporosis mainly affects postmenopausal women and older men. Gastrointestinal hormones released after meal ingestion, such as glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide (GLP)-2, have been shown to regulate bone turnover. However, whether GLP-1, another important gastrointestinal hormone, and its analogues also have antiosteoporotic effects, especially in aged postmenopausal situation, has not been confirmed. In the present study, we evaluated the effects of the GLP-1 receptor agonist exendin-4 on ovariectomy (OVX)-induced osteoporosis in old rats. Twelve-month-old female Sprague-Dawley rats were subjected to OVX, and exendin-4 was administrated 4 weeks after the surgery and lasted for 16 weeks. Bone characters and related serum and gene biomarkers were analyzed. Sixteen weeks of treatment with exendin-4 slowed down body weight gain by decreasing fat mass and prevented the loss of bone mass in old OVX rats. Exendin-4 also enhanced bone strength and prevented the deterioration of trabecular microarchitecture. Moreover, exendin-4 decreased the urinary deoxypyridinoline (DPD)/creatinine ratio and serum C-terminal cross-linked telopeptides of type I collagen (CTX-I) and increased serum alkaline phosphatase (ALP), osteocalcin (OC), and N-terminal propeptide of type 1 procollagen (P1NP) levels, key biochemical markers of bone turnover. Interestingly, gene expression results further showed that exendin-4 not only inhibited bone resorption by increasing the osteoprotegerin (OPG)/receptor activator of NF-κB ligand (RANKL) ratio, but also promoted bone formation by increasing the expression of OC, Col1, Runx2, and ALP, which exhibited dual regulatory effects on bone turnover as compared with previous antiosteoporotic agents. In conclusion, these findings demonstrated for the first time the antiosteoporotic effects of exendin-4 in old OVX rats and that it might be a potential candidate for treatment of aged postmenopausal osteoporosis.
authors: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, China.
authors: Xue
authors: X
authors: Ma
authors: Jingru
authors: J
authors: Meng
authors: Min
authors: M
authors: Jia
authors: Long
authors: L
authors: Bi
authors: Ying
authors: Y
authors: Zhou
authors: Yukun
authors: Y
authors: Wang
authors: Jing
authors: J
authors: Hu
authors: Gonghao
authors: G
authors: He
authors: Xiaoxing
authors: X
authors: Luo
mesh_terms: D000469:Alkaline Phosphatase / Q000097:blood; D000596:Amino Acids / Q000652:urine; D000818:Animals; D024042:Collagen Type I / Q000097:blood; D050659:Core Binding Factor Alpha 1 Subunit / Q000096:biosynthesis; D003404:Creatinine / Q000652:urine; D000077270:Exenatide; D005260:Female; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008297:Male; D015675:Osteocalcin; D010024:Osteoporosis / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D010052:Ovariectomy; D010455:Peptides / Q000097:blood / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018027:Receptors, Glucagon / Q000819:agonists*; D013997:Time Factors; D014688:Venoms / Q000494:pharmacology*
chemical_list: D000596:Amino Acids; D024042:Collagen Type I; D050659:Core Binding Factor Alpha 1 Subunit; C000593833:GLP1R protein, human; C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; D010455:Peptides; D018027:Receptors, Glucagon; C493717:Runx2 protein, rat; D014688:Venoms; C052929:collagen type I trimeric cross-linked peptide; D015675:Osteocalcin; C036020:deoxypyridinoline; D000077270:Exenatide; D003404:Creatinine; D000469:Alkaline Phosphatase