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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.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Ovariectomy was utilized as a model of perimenopausal and postmenopausal osteoporosis. A total of 100\u00a0mg\/kg melatonin, or solvent alone, was added to the drinking water of the rats over 8\u00a0weeks. Perimenopausal rats immediately received intervention following ovariectomy while postmenopausal rats received intervention 8\u00a0weeks 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 (<jats:italic>Runx2<\/jats:italic>, <jats:italic>Sp7<\/jats:italic>) were quantified by real-time quantitative PCR. Alkaline phosphatase (ALP) activity and the gene expression (<jats:italic>Col1a1<\/jats:italic>, <jats:italic>Runx2<\/jats:italic>, <jats:italic>Alpl<\/jats:italic>, and <jats:italic>Bglap<\/jats:italic>) 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.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>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 <jats:italic>Runx2<\/jats:italic> and <jats:italic>Sp7<\/jats:italic> in normal and postmenopausal rats, the opposite of the markers in perimenopausal rats. In vitro study demonstrated that 100\u00a0\u03bcmol\/L melatonin increased the mRNA expression of <jats:italic>Col1a1<\/jats:italic>, <jats:italic>Runx2<\/jats:italic>, and <jats:italic>Alpl<\/jats:italic> three and\/or seven days after intervention, and <jats:italic>Alpl<\/jats:italic> and <jats:italic>Bglap<\/jats:italic> 14 d after intervention. Melatonin increased ALP activity and the extent of ALP and matrix mineralization in the late stage of osteogenesis.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>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.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12967-022-03341-7","type":"journal-article","created":{"date-parts":[[2022,3,16]],"date-time":"2022-03-16T11:03:50Z","timestamp":1647428630000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Melatonin increases bone mass in normal, perimenopausal, and postmenopausal osteoporotic rats via the promotion of osteogenesis"],"prefix":"10.1186","volume":"20","author":[{"given":"Huanshuai","family":"Guan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Kong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Run","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruomu","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanzhi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qilu","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Jiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutian","family":"Lei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangze","family":"Xing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunzheng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0466-2875","authenticated-orcid":false,"given":"Pei","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,3,16]]},"reference":[{"issue":"8","key":"3341_CR1","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1038\/nrrheum.2015.48","volume":"11","author":"G Hendrickx","year":"2015","unstructured":"Hendrickx G, Boudin E, Van Hul W. 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