Melatonin increases bone mass in normal, perimenopausal, and postmenopausal osteoporotic rats via the promotion of osteogenesis
Abstract Background Osteoporosis is a disease threatening the health of millions of individuals. Melatonin is found to be a potential anti-osteoporosis drug. However, whether melatonin plays a role against osteoporosis at different stages of the menopause and the underlying mechanisms are unknown. M...
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| Format: | Article |
| Language: | English |
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BMC
2022-03-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-022-03341-7 |
| _version_ | 1818571753962602496 |
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| author | Huanshuai Guan Ning Kong Run Tian Ruomu Cao Guanzhi Liu Yiyang Li Qilu Wei Ming Jiao Yutian Lei Fangze Xing Peng Tian Kunzheng Wang Pei Yang |
| author_facet | Huanshuai Guan Ning Kong Run Tian Ruomu Cao Guanzhi Liu Yiyang Li Qilu Wei Ming Jiao Yutian Lei Fangze Xing Peng Tian Kunzheng Wang Pei Yang |
| author_sort | Huanshuai Guan |
| collection | DOAJ |
| description | Abstract Background Osteoporosis is a disease threatening the health of millions of individuals. Melatonin is found to be a potential anti-osteoporosis drug. However, whether melatonin plays a role against osteoporosis at different stages of the menopause and the underlying mechanisms are unknown. Methods Ovariectomy was utilized as a model of perimenopausal and postmenopausal osteoporosis. A total of 100 mg/kg melatonin, or solvent alone, was added to the drinking water of the rats over 8 weeks. Perimenopausal rats immediately received intervention following ovariectomy while postmenopausal rats received intervention 8 weeks after ovariectomy. All rats underwent overdose anesthesia following intervention after which blood samples and femurs were collected for further analysis. Rat femurs were scanned using micro-CT and examined histologically. The serum levels of melatonin and osteogenic biochemical markers were measured and the expression of osteogenesis-associated genes (Runx2, Sp7) were quantified by real-time quantitative PCR. Alkaline phosphatase (ALP) activity and the gene expression (Col1a1, Runx2, Alpl, and Bglap) were measured after bone marrow mesenchymal stem cells (BMSCs) were osteogenically induced, both with and without melatonin in vitro. ALP staining and Alizarin Red S staining were used to identify osteogenesis. Results Analysis by micro-CT and histological staining demonstrated that bone mass decreased and bone microarchitecture deteriorated over time after ovariectomy. Intervention with melatonin increased bone mass in normal, perimenopausal, and postmenopausal osteoporotic rats. Serum levels of ALP continuously increased after ovariectomy while osteocalcin levels initially rose, then decreased. Melatonin increased the serum levels of ALP and osteocalcin and mRNA expression levels of Runx2 and Sp7 in normal and postmenopausal rats, the opposite of the markers in perimenopausal rats. In vitro study demonstrated that 100 μmol/L melatonin increased the mRNA expression of Col1a1, Runx2, and Alpl three and/or seven days after intervention, and Alpl and Bglap 14 d after intervention. Melatonin increased ALP activity and the extent of ALP and matrix mineralization in the late stage of osteogenesis. Conclusions Bone mass continuously decreased after ovariectomy, while melatonin increased bone mass and ameliorated bone metabolism in normal, perimenopausal, and postmenopausal osteoporotic rats due to the induction of osteogenic differentiation in BMSCs. |
| first_indexed | 2024-12-14T18:48:31Z |
| format | Article |
| id | doaj.art-bccbeb5ceb6a41729a922221e805171e |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-12-14T18:48:31Z |
| publishDate | 2022-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-bccbeb5ceb6a41729a922221e805171e2022-12-21T22:51:20ZengBMCJournal of Translational Medicine1479-58762022-03-0120111510.1186/s12967-022-03341-7Melatonin increases bone mass in normal, perimenopausal, and postmenopausal osteoporotic rats via the promotion of osteogenesisHuanshuai Guan0Ning Kong1Run Tian2Ruomu Cao3Guanzhi Liu4Yiyang Li5Qilu Wei6Ming Jiao7Yutian Lei8Fangze Xing9Peng Tian10Kunzheng Wang11Pei Yang12Bone and Joint Surgery Center, The Second Affiliated Hospital of Xi’an Jiaotong UniversityBone and Joint Surgery Center, The Second Affiliated Hospital of Xi’an Jiaotong UniversityBone and Joint Surgery Center, The Second Affiliated Hospital of Xi’an Jiaotong UniversityBone and Joint Surgery Center, The Second Affiliated Hospital of Xi’an Jiaotong UniversityBone and Joint Surgery Center, The Second Affiliated Hospital of Xi’an Jiaotong UniversityBone and Joint Surgery Center, The Second Affiliated Hospital of Xi’an Jiaotong UniversityBone and Joint Surgery Center, The Second Affiliated Hospital of Xi’an Jiaotong UniversityBone and Joint Surgery Center, The Second Affiliated Hospital of Xi’an Jiaotong UniversityBone and Joint Surgery Center, The Second Affiliated Hospital of Xi’an Jiaotong UniversityBone and Joint Surgery Center, The Second Affiliated Hospital of Xi’an Jiaotong UniversityBone and Joint Surgery Center, The Second Affiliated Hospital of Xi’an Jiaotong UniversityBone and Joint Surgery Center, The Second Affiliated Hospital of Xi’an Jiaotong UniversityBone and Joint Surgery Center, The Second Affiliated Hospital of Xi’an Jiaotong UniversityAbstract Background Osteoporosis is a disease threatening the health of millions of individuals. Melatonin is found to be a potential anti-osteoporosis drug. However, whether melatonin plays a role against osteoporosis at different stages of the menopause and the underlying mechanisms are unknown. Methods Ovariectomy was utilized as a model of perimenopausal and postmenopausal osteoporosis. A total of 100 mg/kg melatonin, or solvent alone, was added to the drinking water of the rats over 8 weeks. Perimenopausal rats immediately received intervention following ovariectomy while postmenopausal rats received intervention 8 weeks after ovariectomy. All rats underwent overdose anesthesia following intervention after which blood samples and femurs were collected for further analysis. Rat femurs were scanned using micro-CT and examined histologically. The serum levels of melatonin and osteogenic biochemical markers were measured and the expression of osteogenesis-associated genes (Runx2, Sp7) were quantified by real-time quantitative PCR. Alkaline phosphatase (ALP) activity and the gene expression (Col1a1, Runx2, Alpl, and Bglap) were measured after bone marrow mesenchymal stem cells (BMSCs) were osteogenically induced, both with and without melatonin in vitro. ALP staining and Alizarin Red S staining were used to identify osteogenesis. Results Analysis by micro-CT and histological staining demonstrated that bone mass decreased and bone microarchitecture deteriorated over time after ovariectomy. Intervention with melatonin increased bone mass in normal, perimenopausal, and postmenopausal osteoporotic rats. Serum levels of ALP continuously increased after ovariectomy while osteocalcin levels initially rose, then decreased. Melatonin increased the serum levels of ALP and osteocalcin and mRNA expression levels of Runx2 and Sp7 in normal and postmenopausal rats, the opposite of the markers in perimenopausal rats. In vitro study demonstrated that 100 μmol/L melatonin increased the mRNA expression of Col1a1, Runx2, and Alpl three and/or seven days after intervention, and Alpl and Bglap 14 d after intervention. Melatonin increased ALP activity and the extent of ALP and matrix mineralization in the late stage of osteogenesis. Conclusions Bone mass continuously decreased after ovariectomy, while melatonin increased bone mass and ameliorated bone metabolism in normal, perimenopausal, and postmenopausal osteoporotic rats due to the induction of osteogenic differentiation in BMSCs.https://doi.org/10.1186/s12967-022-03341-7MelatoninDifferent stages of the menopauseOsteoporosisOsteogenesisBone marrow mesenchymal stem cells |
| spellingShingle | Huanshuai Guan Ning Kong Run Tian Ruomu Cao Guanzhi Liu Yiyang Li Qilu Wei Ming Jiao Yutian Lei Fangze Xing Peng Tian Kunzheng Wang Pei Yang Melatonin increases bone mass in normal, perimenopausal, and postmenopausal osteoporotic rats via the promotion of osteogenesis Journal of Translational Medicine Melatonin Different stages of the menopause Osteoporosis Osteogenesis Bone marrow mesenchymal stem cells |
| title | Melatonin increases bone mass in normal, perimenopausal, and postmenopausal osteoporotic rats via the promotion of osteogenesis |
| title_full | Melatonin increases bone mass in normal, perimenopausal, and postmenopausal osteoporotic rats via the promotion of osteogenesis |
| title_fullStr | Melatonin increases bone mass in normal, perimenopausal, and postmenopausal osteoporotic rats via the promotion of osteogenesis |
| title_full_unstemmed | Melatonin increases bone mass in normal, perimenopausal, and postmenopausal osteoporotic rats via the promotion of osteogenesis |
| title_short | Melatonin increases bone mass in normal, perimenopausal, and postmenopausal osteoporotic rats via the promotion of osteogenesis |
| title_sort | melatonin increases bone mass in normal perimenopausal and postmenopausal osteoporotic rats via the promotion of osteogenesis |
| topic | Melatonin Different stages of the menopause Osteoporosis Osteogenesis Bone marrow mesenchymal stem cells |
| url | https://doi.org/10.1186/s12967-022-03341-7 |
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