Suppression of osteogenic differentiation and mitochondrial function change in human periodontal ligament stem cells by melatonin at physiological levels
N-Acetyl-5-methoxytryptamine (melatonin, MT) at pharmacological concentrations promotes the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells; however, its role at physiological concentrations (1 pM–10 nM) remains unclear. We explored the effects of 1 pM–1 µM MT on the o...
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PeerJ Inc.
2020-03-01
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| author | Miaomiao Zheng Fuping Zhang Wenguo Fan Liulin Jiang Jingzhou Li Shanshan Xie Fang Huang Hongwen He |
| author_facet | Miaomiao Zheng Fuping Zhang Wenguo Fan Liulin Jiang Jingzhou Li Shanshan Xie Fang Huang Hongwen He |
| author_sort | Miaomiao Zheng |
| collection | DOAJ |
| description | N-Acetyl-5-methoxytryptamine (melatonin, MT) at pharmacological concentrations promotes the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells; however, its role at physiological concentrations (1 pM–10 nM) remains unclear. We explored the effects of 1 pM–1 µM MT on the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) and its underlying mitochondrial dynamics-mediated mechanisms. T he PDLSC phenotype was detected by flow cytometry and evaluated for three-line differentiation. Alkaline phosphatase activity assay and Alizarin red staining were used to evaluate osteogenic differentiation. Osteogenesis-related gene and protein expression levels were measured by quantitative reverse transcription -polymerase chain reaction and western blotting. Mitochondrial function assays were performed using reactive oxygen species, ATP and NAD+/NADH kits and molecular mechanisms of mitochondrial dynamics-related proteins were assessed by western blotting. Our results have shown that physiological MT concentrations induced differentiation of hPDLSCs and down-regulated osteopontin (OPN) and osteocalcin (OCN) expression levels, which were restored or even up-regulated by 1 µM MT (lowest pharmacological concentration). Compared to the osteogenic induction alone, this treatment decreased the intracellular ATP content, whereas the intracellular reactive oxygen species level and NAD+/NADH ratio were increased. Mitochondrial function- and dynamics-related protein expression levels were consistent with those of osteogenic genes following osteogenic induction and MT treatment of hPDLSCs at various physiological concentrations. Physiological MT concentrations inhibited the osteogenic differentiation of hPDLSCs and simultaneously altered mitochondrial function. These findings provide insights into the stem cell tissue engineering and functions of MT. |
| first_indexed | 2024-03-09T07:28:46Z |
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| id | doaj.art-fb7d2ecb45464dc79511dee9c7eb7e08 |
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| issn | 2167-8359 |
| language | English |
| last_indexed | 2024-03-09T07:28:46Z |
| publishDate | 2020-03-01 |
| publisher | PeerJ Inc. |
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| spelling | doaj.art-fb7d2ecb45464dc79511dee9c7eb7e082023-12-03T06:48:28ZengPeerJ Inc.PeerJ2167-83592020-03-018e866310.7717/peerj.8663Suppression of osteogenic differentiation and mitochondrial function change in human periodontal ligament stem cells by melatonin at physiological levelsMiaomiao Zheng0Fuping Zhang1Wenguo Fan2Liulin Jiang3Jingzhou Li4Shanshan Xie5Fang Huang6Hongwen He7Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, ChinaGuanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, ChinaGuanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, ChinaGuanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, ChinaGuanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, ChinaGuanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, ChinaGuanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, ChinaGuanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, ChinaN-Acetyl-5-methoxytryptamine (melatonin, MT) at pharmacological concentrations promotes the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells; however, its role at physiological concentrations (1 pM–10 nM) remains unclear. We explored the effects of 1 pM–1 µM MT on the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) and its underlying mitochondrial dynamics-mediated mechanisms. T he PDLSC phenotype was detected by flow cytometry and evaluated for three-line differentiation. Alkaline phosphatase activity assay and Alizarin red staining were used to evaluate osteogenic differentiation. Osteogenesis-related gene and protein expression levels were measured by quantitative reverse transcription -polymerase chain reaction and western blotting. Mitochondrial function assays were performed using reactive oxygen species, ATP and NAD+/NADH kits and molecular mechanisms of mitochondrial dynamics-related proteins were assessed by western blotting. Our results have shown that physiological MT concentrations induced differentiation of hPDLSCs and down-regulated osteopontin (OPN) and osteocalcin (OCN) expression levels, which were restored or even up-regulated by 1 µM MT (lowest pharmacological concentration). Compared to the osteogenic induction alone, this treatment decreased the intracellular ATP content, whereas the intracellular reactive oxygen species level and NAD+/NADH ratio were increased. Mitochondrial function- and dynamics-related protein expression levels were consistent with those of osteogenic genes following osteogenic induction and MT treatment of hPDLSCs at various physiological concentrations. Physiological MT concentrations inhibited the osteogenic differentiation of hPDLSCs and simultaneously altered mitochondrial function. These findings provide insights into the stem cell tissue engineering and functions of MT.https://peerj.com/articles/8663.pdfMelatoninMitochondrial functionMitochondrial dynamics Osteogenic differentiationPeriodontal ligament stem cell |
| spellingShingle | Miaomiao Zheng Fuping Zhang Wenguo Fan Liulin Jiang Jingzhou Li Shanshan Xie Fang Huang Hongwen He Suppression of osteogenic differentiation and mitochondrial function change in human periodontal ligament stem cells by melatonin at physiological levels PeerJ Melatonin Mitochondrial function Mitochondrial dynamics Osteogenic differentiation Periodontal ligament stem cell |
| title | Suppression of osteogenic differentiation and mitochondrial function change in human periodontal ligament stem cells by melatonin at physiological levels |
| title_full | Suppression of osteogenic differentiation and mitochondrial function change in human periodontal ligament stem cells by melatonin at physiological levels |
| title_fullStr | Suppression of osteogenic differentiation and mitochondrial function change in human periodontal ligament stem cells by melatonin at physiological levels |
| title_full_unstemmed | Suppression of osteogenic differentiation and mitochondrial function change in human periodontal ligament stem cells by melatonin at physiological levels |
| title_short | Suppression of osteogenic differentiation and mitochondrial function change in human periodontal ligament stem cells by melatonin at physiological levels |
| title_sort | suppression of osteogenic differentiation and mitochondrial function change in human periodontal ligament stem cells by melatonin at physiological levels |
| topic | Melatonin Mitochondrial function Mitochondrial dynamics Osteogenic differentiation Periodontal ligament stem cell |
| url | https://peerj.com/articles/8663.pdf |
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