<span style="font-variant: small-caps">l</span>-Quebrachitol Promotes the Proliferation, Differentiation, and Mineralization of MC3T3-E1 Cells: Involvement of the BMP-2/Runx2/MAPK/Wnt/β-Catenin Signaling Pathway
Osteoporosis is widely recognized as a major health problem caused by an inappropriate rate of bone resorption compared to bone formation. Previously we showed that <span style="font-variant: small-caps;">d</span>-pinitol inhibits osteoclastogenesis but has no effect on osteobl...
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| Format: | Article |
| Language: | English |
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MDPI AG
2018-11-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/23/12/3086 |
| _version_ | 1811284119221436416 |
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| author | Thanintorn Yodthong Ureporn Kedjarune-Leggat Carl Smythe Rapepun Wititsuwannakul Thanawat Pitakpornpreecha |
| author_facet | Thanintorn Yodthong Ureporn Kedjarune-Leggat Carl Smythe Rapepun Wititsuwannakul Thanawat Pitakpornpreecha |
| author_sort | Thanintorn Yodthong |
| collection | DOAJ |
| description | Osteoporosis is widely recognized as a major health problem caused by an inappropriate rate of bone resorption compared to bone formation. Previously we showed that <span style="font-variant: small-caps;">d</span>-pinitol inhibits osteoclastogenesis but has no effect on osteoblastogenesis. However, the effect on osteoblast differentiation of its isomer, <span style="font-variant: small-caps;">l</span>-quebrachitol, has not yet been reported. The purpose of this study was, therefore, to investigate whether <span style="font-variant: small-caps;">l</span>-quebrachitol promotes the osteoblastogenesis of pre-osteoblastic MC3T3-E1 cells. Moreover, the molecular mechanism of action of <span style="font-variant: small-caps;">l</span>-quebrachitol was further explored. Here, it is shown for the first time that <span style="font-variant: small-caps;">l</span>-quebrachitol significantly promotes proliferation and cell DNA synthesis. It also enhances mineralization accompanied by increases in mRNA expression of bone matrix proteins including alkaline phosphatase (ALP), collagen type I (ColI), osteocalcin (OCN), and osteopontin (OPN). In addition, <span style="font-variant: small-caps;">l</span>-quebrachitol upregulates the mRNA and protein expression of bone morphogenetic protein-2 (BMP-2) and runt-related transcription factor-2 (Runx2), while down-regulating the receptor activator of the nuclear factor-<i>κ</i>B ligand (RANKL) mRNA level. Moreover, the expression of regulatory genes associated with the mitogen-activated protein kinase (MAPK) and wingless-type MMTV integration site (Wnt)/β-catenin signaling pathways are also upregulated. These findings indicate that <span style="font-variant: small-caps;">l</span>-quebrachitol may promote osteoblastogenesis by triggering the BMP-2-response as well as the Runx2, MAPK, and Wnt/β-catenin signaling pathway. |
| first_indexed | 2024-04-13T02:23:50Z |
| format | Article |
| id | doaj.art-73aeabc577e64c75ac178bfce2b659b8 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-04-13T02:23:50Z |
| publishDate | 2018-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-73aeabc577e64c75ac178bfce2b659b82022-12-22T03:06:51ZengMDPI AGMolecules1420-30492018-11-012312308610.3390/molecules23123086molecules23123086<span style="font-variant: small-caps">l</span>-Quebrachitol Promotes the Proliferation, Differentiation, and Mineralization of MC3T3-E1 Cells: Involvement of the BMP-2/Runx2/MAPK/Wnt/β-Catenin Signaling PathwayThanintorn Yodthong0Ureporn Kedjarune-Leggat1Carl Smythe2Rapepun Wititsuwannakul3Thanawat Pitakpornpreecha4Department of Biochemistry, Faculty of Science, Prince of Songkla University, Hat-Yai, Songkhla 90110, ThailandDepartment of Oral biology and Occlusion, Faculty of Dentistry, Prince of Songkla University, Hat-Yai, Songkhla 90110, ThailandDepartment of Biomedical Science, University of Sheffield, Sheffield, England S10 2TN, UKCenter of Excellence in Natural Rubber Latex Biotechnology Research and Development, Prince of Songkla University, Hat-Yai, Songkhla 90110, ThailandDepartment of Biochemistry, Faculty of Science, Prince of Songkla University, Hat-Yai, Songkhla 90110, ThailandOsteoporosis is widely recognized as a major health problem caused by an inappropriate rate of bone resorption compared to bone formation. Previously we showed that <span style="font-variant: small-caps;">d</span>-pinitol inhibits osteoclastogenesis but has no effect on osteoblastogenesis. However, the effect on osteoblast differentiation of its isomer, <span style="font-variant: small-caps;">l</span>-quebrachitol, has not yet been reported. The purpose of this study was, therefore, to investigate whether <span style="font-variant: small-caps;">l</span>-quebrachitol promotes the osteoblastogenesis of pre-osteoblastic MC3T3-E1 cells. Moreover, the molecular mechanism of action of <span style="font-variant: small-caps;">l</span>-quebrachitol was further explored. Here, it is shown for the first time that <span style="font-variant: small-caps;">l</span>-quebrachitol significantly promotes proliferation and cell DNA synthesis. It also enhances mineralization accompanied by increases in mRNA expression of bone matrix proteins including alkaline phosphatase (ALP), collagen type I (ColI), osteocalcin (OCN), and osteopontin (OPN). In addition, <span style="font-variant: small-caps;">l</span>-quebrachitol upregulates the mRNA and protein expression of bone morphogenetic protein-2 (BMP-2) and runt-related transcription factor-2 (Runx2), while down-regulating the receptor activator of the nuclear factor-<i>κ</i>B ligand (RANKL) mRNA level. Moreover, the expression of regulatory genes associated with the mitogen-activated protein kinase (MAPK) and wingless-type MMTV integration site (Wnt)/β-catenin signaling pathways are also upregulated. These findings indicate that <span style="font-variant: small-caps;">l</span>-quebrachitol may promote osteoblastogenesis by triggering the BMP-2-response as well as the Runx2, MAPK, and Wnt/β-catenin signaling pathway.https://www.mdpi.com/1420-3049/23/12/3086<span style="font-variant: small-caps">l</span>-quebrachitolOsteoblastogenesisWnt/β-CateninBMP-2Runx2MAPK |
| spellingShingle | Thanintorn Yodthong Ureporn Kedjarune-Leggat Carl Smythe Rapepun Wititsuwannakul Thanawat Pitakpornpreecha <span style="font-variant: small-caps">l</span>-Quebrachitol Promotes the Proliferation, Differentiation, and Mineralization of MC3T3-E1 Cells: Involvement of the BMP-2/Runx2/MAPK/Wnt/β-Catenin Signaling Pathway Molecules <span style="font-variant: small-caps">l</span>-quebrachitol Osteoblastogenesis Wnt/β-Catenin BMP-2 Runx2 MAPK |
| title | <span style="font-variant: small-caps">l</span>-Quebrachitol Promotes the Proliferation, Differentiation, and Mineralization of MC3T3-E1 Cells: Involvement of the BMP-2/Runx2/MAPK/Wnt/β-Catenin Signaling Pathway |
| title_full | <span style="font-variant: small-caps">l</span>-Quebrachitol Promotes the Proliferation, Differentiation, and Mineralization of MC3T3-E1 Cells: Involvement of the BMP-2/Runx2/MAPK/Wnt/β-Catenin Signaling Pathway |
| title_fullStr | <span style="font-variant: small-caps">l</span>-Quebrachitol Promotes the Proliferation, Differentiation, and Mineralization of MC3T3-E1 Cells: Involvement of the BMP-2/Runx2/MAPK/Wnt/β-Catenin Signaling Pathway |
| title_full_unstemmed | <span style="font-variant: small-caps">l</span>-Quebrachitol Promotes the Proliferation, Differentiation, and Mineralization of MC3T3-E1 Cells: Involvement of the BMP-2/Runx2/MAPK/Wnt/β-Catenin Signaling Pathway |
| title_short | <span style="font-variant: small-caps">l</span>-Quebrachitol Promotes the Proliferation, Differentiation, and Mineralization of MC3T3-E1 Cells: Involvement of the BMP-2/Runx2/MAPK/Wnt/β-Catenin Signaling Pathway |
| title_sort | span style font variant small caps l span quebrachitol promotes the proliferation differentiation and mineralization of mc3t3 e1 cells involvement of the bmp 2 runx2 mapk wnt β catenin signaling pathway |
| topic | <span style="font-variant: small-caps">l</span>-quebrachitol Osteoblastogenesis Wnt/β-Catenin BMP-2 Runx2 MAPK |
| url | https://www.mdpi.com/1420-3049/23/12/3086 |
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