El-Marasy Salma Ahmed, Abdel-Rahman Rehab F, Abd-Elsalam Reham M, Ogaly Hanan A, Allam Rasha M
Department of Pharmacology, Medical Research and Clinical Studies Institute, National Research Centre, Giza, Egypt.
Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.
Naunyn Schmiedebergs Arch Pharmacol. 2025 May 21. doi: 10.1007/s00210-025-04145-4.
This study examines the potential anti-osteoporotic effect of sitagliptin in osteoporosis instigated by ovariectomy (OVX) in rats. Rats were assigned into 4 groups: Sham-operated, OVX group, and OVX rats orally treated with sitagliptin (10, 20 mg/kg), respectively, after 8 weeks of OVX for 4 weeks. Biochemical, real-time polymerase chain reaction, histopathological, and immunohistochemical analyses of bone resorption and formation were conducted. Sitagliptin ameliorated bone mineral density (BMD), restored calcium and phosphorus levels in OVX rats, elevated catalase and decreased malondialdehyde, reduced receptor activator of NF-κB ligand (RANKL), elevated osteoprotegerin (OPG), and reduced tartrate-resistant acid phosphatase (TRAP) femur contents. Sitagliptin mitigated variations in mRNA expressions of RUNX2 and protein kinase B (AKT) in femur tissue. Moreover, sitagliptin reduced caspase-3 protein expression and improved bone histomorphology and mechanical properties. Sitagliptin's anti-oxidant activity mediated its anti-osteoporotic effect in OVX rats via modulation of RUNX2, downregulation of RANKL/OPG, AKT pathways, apoptosis, and histomorphometry alterations revealing attenuation of osteoclastogenesis and promotion of osteoblast formation.
本研究考察了西他列汀对大鼠卵巢切除（OVX）所致骨质疏松的潜在抗骨质疏松作用。将大鼠分为4组：假手术组、OVX组以及OVX术后8周给予西他列汀（10、20mg/kg）口服治疗4周的大鼠组。进行了骨吸收和形成的生化、实时聚合酶链反应、组织病理学及免疫组化分析。西他列汀改善了OVX大鼠的骨矿物质密度（BMD），恢复了钙和磷水平，提高了过氧化氢酶水平并降低了丙二醛水平，降低了核因子κB受体活化因子配体（RANKL）水平，提高了骨保护素（OPG）水平，并降低了股骨中抗酒石酸酸性磷酸酶（TRAP）含量。西他列汀减轻了股骨组织中RUNX2和蛋白激酶B（AKT）mRNA表达的变化。此外，西他列汀降低了半胱天冬酶-3蛋白表达，改善了骨组织形态学和力学性能。西他列汀的抗氧化活性通过调节RUNX2、下调RANKL/OPG、AKT通路、细胞凋亡以及组织形态计量学改变介导其对OVX大鼠的抗骨质疏松作用，这些改变显示破骨细胞生成减弱且成骨细胞形成增加。
