All-trans retinoic acid can antagonize osteoblastogenesis induced by different BMPs irrespective of their dimerization types and dose-efficiencies
Yi Liu,1,* Xiaoqing Ma,2,* Jing Guo,1 Zhen Lin,3 Miao Zhou,1 Wenjuan Bi,4 Jinsong Liu,5 Jingxiao Wang,6 Haiping Lu,7,* Gang Wu8,* 1Key Laboratory of Oral Medicine, Guangzhou Institute of Oral Disease, Stomatology Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou 5101...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2018-10-01
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| Series: | Drug Design, Development and Therapy |
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| Online Access: | https://www.dovepress.com/all-trans-retinoic-acid-can-antagonize-osteoblastogenesis-induced-by-d-peer-reviewed-article-DDDT |
| _version_ | 1818128544924958720 |
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| author | Liu Y Ma X Guo J Lin Z Zhou M Bi W Liu J Wang J Lu H Wu G |
| author_facet | Liu Y Ma X Guo J Lin Z Zhou M Bi W Liu J Wang J Lu H Wu G |
| author_sort | Liu Y |
| collection | DOAJ |
| description | Yi Liu,1,* Xiaoqing Ma,2,* Jing Guo,1 Zhen Lin,3 Miao Zhou,1 Wenjuan Bi,4 Jinsong Liu,5 Jingxiao Wang,6 Haiping Lu,7,* Gang Wu8,* 1Key Laboratory of Oral Medicine, Guangzhou Institute of Oral Disease, Stomatology Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou 510140, China; 2Shanghai Xuhui District Dental Center, Shanghai 200032, China; 3Department of Orthopedics, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China; 4College of Stomatology, North China University of Science and Technology, Tangshan 063000, China; 5School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou 325000, China; 6The First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325000, China; 7School of Stomatology, Zhejiang Chinese Medical University, Hangzhou 310053, China; 8Department of Oral Implantology and Prosthetic Dentistry, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, 1081LA Amsterdam, the Netherlands *These authors contributed equally to this work Introduction: Alcoholism can lead to low mineral density, compromised regenerative bone capacity and delayed osteointegration of dental implants. This may be partially attributed to the inhibitive effect of all-trans retinoic acid (ATRA), a metabolite of alcohol, on osteoblastogenesis. Our previous studies demonstrated that heterodimeric bone morphogenetic protein 2/7 (BMP2/7) was a more potent BMP than homodimeric BMP2 or BMP7, and could antagonize the inhibitive effect of ATRA to rescue osteoblastogenesis.Materials and methods: In this study, we compared the effectiveness of BMP2/7, BMP2 and BMP7 in restoring osteoblastogenesis of murine preosteoblasts upon inhibition with 1 µM ATRA, and we further analyzed the potential mechanisms. We measured the following parameters: cell viability, ALP, OCN, mineralization, the expression of osteogenic differentiation marker genes (Collagen I, ALP and OCN) and the expression of BMP signaling key genes (Dlx5, Runx2, Osterix and Smad1).Results: BMP2/7 treatment alone induced significantly higher osteoblastogenesis compared to BMP2 and BMP7. When cells were treated by ATRA, BMP2/7 was superior only in rescuing cell viability and ALP activity, compared to BMP2 or BMP7. However, BMP2/7 was not superior to BMP2 or BMP7 in restoring OCN expression and extracellular mineralized nodules, or in rescuing expression of two key osteogenic genes, Dlx5 and Runx2. Irrespective of their dimeric types or potency, the selected BMPs could antagonize the inhibitory effect of ATRA on osteoblastogenesis.Conclusion: The presence of ATRA, BMP2/7 still induced significantly higher cell viability and early differentiation than the homodimers. However, ATRA significantly attenuated the advantages of BMP2/7 in inducing late and final osteoblastogenic differentiation over the homodimers. Keywords: heterodimeric, homodimeric, bone morphogenetic protein, osteoblastogenesis, all-trans retinoic acid |
| first_indexed | 2024-12-11T07:34:57Z |
| format | Article |
| id | doaj.art-b796d555b4344c31a5801b5c56f8416d |
| institution | Directory Open Access Journal |
| issn | 1177-8881 |
| language | English |
| last_indexed | 2024-12-11T07:34:57Z |
| publishDate | 2018-10-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Drug Design, Development and Therapy |
| spelling | doaj.art-b796d555b4344c31a5801b5c56f8416d2022-12-22T01:15:44ZengDove Medical PressDrug Design, Development and Therapy1177-88812018-10-01Volume 123419343041332All-trans retinoic acid can antagonize osteoblastogenesis induced by different BMPs irrespective of their dimerization types and dose-efficienciesLiu YMa XGuo JLin ZZhou MBi WLiu JWang JLu HWu GYi Liu,1,* Xiaoqing Ma,2,* Jing Guo,1 Zhen Lin,3 Miao Zhou,1 Wenjuan Bi,4 Jinsong Liu,5 Jingxiao Wang,6 Haiping Lu,7,* Gang Wu8,* 1Key Laboratory of Oral Medicine, Guangzhou Institute of Oral Disease, Stomatology Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou 510140, China; 2Shanghai Xuhui District Dental Center, Shanghai 200032, China; 3Department of Orthopedics, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China; 4College of Stomatology, North China University of Science and Technology, Tangshan 063000, China; 5School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou 325000, China; 6The First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325000, China; 7School of Stomatology, Zhejiang Chinese Medical University, Hangzhou 310053, China; 8Department of Oral Implantology and Prosthetic Dentistry, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, 1081LA Amsterdam, the Netherlands *These authors contributed equally to this work Introduction: Alcoholism can lead to low mineral density, compromised regenerative bone capacity and delayed osteointegration of dental implants. This may be partially attributed to the inhibitive effect of all-trans retinoic acid (ATRA), a metabolite of alcohol, on osteoblastogenesis. Our previous studies demonstrated that heterodimeric bone morphogenetic protein 2/7 (BMP2/7) was a more potent BMP than homodimeric BMP2 or BMP7, and could antagonize the inhibitive effect of ATRA to rescue osteoblastogenesis.Materials and methods: In this study, we compared the effectiveness of BMP2/7, BMP2 and BMP7 in restoring osteoblastogenesis of murine preosteoblasts upon inhibition with 1 µM ATRA, and we further analyzed the potential mechanisms. We measured the following parameters: cell viability, ALP, OCN, mineralization, the expression of osteogenic differentiation marker genes (Collagen I, ALP and OCN) and the expression of BMP signaling key genes (Dlx5, Runx2, Osterix and Smad1).Results: BMP2/7 treatment alone induced significantly higher osteoblastogenesis compared to BMP2 and BMP7. When cells were treated by ATRA, BMP2/7 was superior only in rescuing cell viability and ALP activity, compared to BMP2 or BMP7. However, BMP2/7 was not superior to BMP2 or BMP7 in restoring OCN expression and extracellular mineralized nodules, or in rescuing expression of two key osteogenic genes, Dlx5 and Runx2. Irrespective of their dimeric types or potency, the selected BMPs could antagonize the inhibitory effect of ATRA on osteoblastogenesis.Conclusion: The presence of ATRA, BMP2/7 still induced significantly higher cell viability and early differentiation than the homodimers. However, ATRA significantly attenuated the advantages of BMP2/7 in inducing late and final osteoblastogenic differentiation over the homodimers. Keywords: heterodimeric, homodimeric, bone morphogenetic protein, osteoblastogenesis, all-trans retinoic acidhttps://www.dovepress.com/all-trans-retinoic-acid-can-antagonize-osteoblastogenesis-induced-by-d-peer-reviewed-article-DDDTHeterodimericHomodimericBone morphogenetic proteinOsteoblastogenesisAll-trans retinoic acid. |
| spellingShingle | Liu Y Ma X Guo J Lin Z Zhou M Bi W Liu J Wang J Lu H Wu G All-trans retinoic acid can antagonize osteoblastogenesis induced by different BMPs irrespective of their dimerization types and dose-efficiencies Drug Design, Development and Therapy Heterodimeric Homodimeric Bone morphogenetic protein Osteoblastogenesis All-trans retinoic acid. |
| title | All-trans retinoic acid can antagonize osteoblastogenesis induced by different BMPs irrespective of their dimerization types and dose-efficiencies |
| title_full | All-trans retinoic acid can antagonize osteoblastogenesis induced by different BMPs irrespective of their dimerization types and dose-efficiencies |
| title_fullStr | All-trans retinoic acid can antagonize osteoblastogenesis induced by different BMPs irrespective of their dimerization types and dose-efficiencies |
| title_full_unstemmed | All-trans retinoic acid can antagonize osteoblastogenesis induced by different BMPs irrespective of their dimerization types and dose-efficiencies |
| title_short | All-trans retinoic acid can antagonize osteoblastogenesis induced by different BMPs irrespective of their dimerization types and dose-efficiencies |
| title_sort | all trans retinoic acid can antagonize osteoblastogenesis induced by different bmps irrespective of their dimerization types and dose efficiencies |
| topic | Heterodimeric Homodimeric Bone morphogenetic protein Osteoblastogenesis All-trans retinoic acid. |
| url | https://www.dovepress.com/all-trans-retinoic-acid-can-antagonize-osteoblastogenesis-induced-by-d-peer-reviewed-article-DDDT |
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