Köse, DuyguKöse, AhmetHalıcı, ZekaiGürbüz, Muhammet AliMaman, AdemYayla, Muhammed2022-09-292022-09-292021https://dergipark.org.tr/tr/download/article-file/1775561https://hdl.handle.net/20.500.12868/1713Aim: Melatonin promoted osteoblast differentiation and causes an increase in levels of markers of bone differentiation and proliferation. Ramelteon (RAMEL) activates melatonin receptors and binds to these receptors as non-selective. In this study, we investigated the preventive effects of the melatonin agonist RAMEL on osteoporosis by radiological, histological, and molecularly. Methods: Groups 1: Control, Group 2: Osteoporosis: Overectomized group (OP), Group 3: OP + ramelteon 2 mg/kg, Group 4: OP + ramelteon 4 mg/kg. 24 animals underwent bilateral ovariectomy. RAMEL was administered orally once a day in the prophylactic treatment mode for 8 weeks, 6 weeks after ovariectomy. Results: Fourteen weeks after ovariectomy, there was a significant reduction in femoral bone mineral density (BMD) (g/cm2) in the OP group compared to the control group. Compared to the OP group, RAMEL treatment significantly increased the BMD level (p<0.05). Bone matrix protein 2 (BMP2) and runt-related transcription factor 2 (RUNX2) mRNA levels were significantly lower in the OP group than in the control group (p<0.05). RUNX2 and BMP2 mRNA levels were significantly higher in the RAMEL treatment groups than in the OP group (p<0.05). Conclusion: To take advantage of the peripheral effects of melatonin, RAMEL, a peripheral melatonin agonist, can be used to prevent osteoporosis.eninfo:eu-repo/semantics/openAccessRamelteon, melatonin, osteoporosis, boneRamelteonMelatoninOsteoporosisBoneArticle10.30565/medalanya.93916152164170