The crucial role of beta-catenin in the osteoprotective effect of semaglutide in an ovariectomized rat model of osteoporosis.

Autor: Abo-Elenin MHH; Pharmacology and Toxicology Department, Faculty of Pharmacy, Helwan University, Ein Helwan, Cairo City, Egypt. Mohannad.hakam@pharm.helwan.edu.eg., Kamel R; Pharmacology and Toxicology Department, Faculty of Pharmacy, Helwan University, Ein Helwan, Cairo City, Egypt., Nofal S; Pharmacology and Toxicology Department, Faculty of Pharmacy, Helwan University, Ein Helwan, Cairo City, Egypt., Ahmed AAE; Pharmacology and Toxicology Department, Faculty of Pharmacy, Helwan University, Ein Helwan, Cairo City, Egypt.
Jazyk: angličtina
Zdroj: Naunyn-Schmiedeberg's archives of pharmacology [Naunyn Schmiedebergs Arch Pharmacol] 2024 Sep 10. Date of Electronic Publication: 2024 Sep 10.
DOI: 10.1007/s00210-024-03378-z
Abstrakt: Postmenopausal osteoporosis is a common chronic medical illness resulting from an imbalance between bone resorption and bone formation along with microarchitecture degeneration attributed to estrogen deficiency and often accompanied by other medical conditions such as weight gain, depression, and insomnia. Semaglutide (SEM) is a recently introduced GLP-1 receptor agonist (GLP-1RA) for the treatment of obesity and type 2 diabetes mellitus by mitigating insulin resistance. It has been discovered that the beneficial effects of GLP-1 are associated with alterations in lipolysis, adipogenesis, and anti-inflammatory processes. GLP-1 analogs transmit signals directly to adipose tissue. Mesenchymal stem cells (MSCs) are multidisciplinary cells that originate from bone marrow, migrate to injury sites, and promote bone regeneration. MSCs can differentiate into osteoblasts, adipose cells, and cartilage cells. Our aim is to investigate the role of semaglutide on bone formation and the Wnt signaling pathway. Osteoporosis was induced in female rats by ovariectomy, and the ovariectomized rats were treated with alendronate as standard treatment with a dose of 3 mg/kg orally and semaglutide with two doses (150 mcg/kg and 300 mcg/kg) S.C. for 10 successive weeks. Semaglutide ameliorates bone detrimental changes induced by ovariectomy. It improves bone microarchitecture and preserves bone mineral content. Semaglutide ameliorates ovariectomy-induced osteoporosis and increases the expression of β-catenin, leading to increased bone formation and halted receptor activator of nuclear factor kappa-Β ligand (RANKL's) activation. Semaglutide can be used as a potential prophylactic and therapeutic drug against osteoporosis, possibly by activating Wnt signaling and decreasing bone resorption.
(© 2024. The Author(s).)
Databáze: MEDLINE
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