Bleomycin: A novel osteogenesis inhibitor of dental follicle cells via a TGF‐β1/SMAD7/RUNX2 pathway
Background and Purpose Tooth eruption is a complicated process regulated by the dental follicles (DF). Our recent study discovered that tooth eruption was inhibited upon injection of bleomycin into DF. However, the mechanisms were unknown. Experimental Approach Human dental follicle cells (hDFCs) we...
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| Published in | British journal of pharmacology Vol. 178; no. 2; pp. 312 - 327 |
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| Main Authors | , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
England
Blackwell Publishing Ltd
01.01.2021
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| Subjects | |
| Online Access | Get full text |
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| Abstract | Background and Purpose
Tooth eruption is a complicated process regulated by the dental follicles (DF). Our recent study discovered that tooth eruption was inhibited upon injection of bleomycin into DF. However, the mechanisms were unknown.
Experimental Approach
Human dental follicle cells (hDFCs) were treated by bleomycin or exogenous TGF‐β1 or transfected by plasmids loading SMAD7 or shRNA targeting SMAD7, followed by osteogenesis induction assay and signalling analysis. Human fresh DF tissues and Wistar rats were used to further confirm bleomycin function.
Key Results
Bleomycin decreased expression of RUNX2 and osteogenic genes in hDFCs, reducing osteogenic capacity. TGF‐β1 expression was up‐regulated in bleomycin‐treated hDFCs. The effects of exogenous TGF‐β1 were similar to those of bleomycin in hDFCs. Additionally, compared to SMAD2/3, SMAD7 expression increased more in bleomycin‐ or TGF‐β1‐treated hDFCs. Overexpression of SMAD7 likewise significantly decreased RUNX2 expression and osteogenic capacity of hDFCs. Knockdown of SMAD7 markedly attenuated the inhibitory effects of bleomycin and TGF‐β1 on osteogenic capacity and RUNX2 expression of hDFCs. Most importantly, changes in TGF‐β1, SMAD7, and RUNX2 expressions were similar in the DF of rats and humans treated with bleomycin.
Conclusion and Implications
SMAD7 was a negative regulator of osteogenic differentiation in DFCs through suppressing RUNX2 expression. Bleomycin or TGF‐β1 inhibited osteogenic differentiation of DFCs via a TGF‐β1/SMAD7/RUNX2 pathway. Our findings might be beneficial for enhancing the osteogenic activity of DFCs or inhibiting the eruption of undesirable teeth. |
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| AbstractList | Background and PurposeTooth eruption is a complicated process regulated by the dental follicles (DF). Our recent study discovered that tooth eruption was inhibited upon injection of bleomycin into DF. However, the mechanisms were unknown.Experimental ApproachHuman dental follicle cells (hDFCs) were treated by bleomycin or exogenous TGF‐β1 or transfected by plasmids loading SMAD7 or shRNA targeting SMAD7, followed by osteogenesis induction assay and signalling analysis. Human fresh DF tissues and Wistar rats were used to further confirm bleomycin function.Key ResultsBleomycin decreased expression of RUNX2 and osteogenic genes in hDFCs, reducing osteogenic capacity. TGF‐β1 expression was up‐regulated in bleomycin‐treated hDFCs. The effects of exogenous TGF‐β1 were similar to those of bleomycin in hDFCs. Additionally, compared to SMAD2/3, SMAD7 expression increased more in bleomycin‐ or TGF‐β1‐treated hDFCs. Overexpression of SMAD7 likewise significantly decreased RUNX2 expression and osteogenic capacity of hDFCs. Knockdown of SMAD7 markedly attenuated the inhibitory effects of bleomycin and TGF‐β1 on osteogenic capacity and RUNX2 expression of hDFCs. Most importantly, changes in TGF‐β1, SMAD7, and RUNX2 expressions were similar in the DF of rats and humans treated with bleomycin.Conclusion and ImplicationsSMAD7 was a negative regulator of osteogenic differentiation in DFCs through suppressing RUNX2 expression. Bleomycin or TGF‐β1 inhibited osteogenic differentiation of DFCs via a TGF‐β1/SMAD7/RUNX2 pathway. Our findings might be beneficial for enhancing the osteogenic activity of DFCs or inhibiting the eruption of undesirable teeth. Background and Purpose Tooth eruption is a complicated process regulated by the dental follicles (DF). Our recent study discovered that tooth eruption was inhibited upon injection of bleomycin into DF. However, the mechanisms were unknown. Experimental Approach Human dental follicle cells (hDFCs) were treated by bleomycin or exogenous TGF‐β1 or transfected by plasmids loading SMAD7 or shRNA targeting SMAD7, followed by osteogenesis induction assay and signalling analysis. Human fresh DF tissues and Wistar rats were used to further confirm bleomycin function. Key Results Bleomycin decreased expression of RUNX2 and osteogenic genes in hDFCs, reducing osteogenic capacity. TGF‐β1 expression was up‐regulated in bleomycin‐treated hDFCs. The effects of exogenous TGF‐β1 were similar to those of bleomycin in hDFCs. Additionally, compared to SMAD2/3, SMAD7 expression increased more in bleomycin‐ or TGF‐β1‐treated hDFCs. Overexpression of SMAD7 likewise significantly decreased RUNX2 expression and osteogenic capacity of hDFCs. Knockdown of SMAD7 markedly attenuated the inhibitory effects of bleomycin and TGF‐β1 on osteogenic capacity and RUNX2 expression of hDFCs. Most importantly, changes in TGF‐β1, SMAD7, and RUNX2 expressions were similar in the DF of rats and humans treated with bleomycin. Conclusion and Implications SMAD7 was a negative regulator of osteogenic differentiation in DFCs through suppressing RUNX2 expression. Bleomycin or TGF‐β1 inhibited osteogenic differentiation of DFCs via a TGF‐β1/SMAD7/RUNX2 pathway. Our findings might be beneficial for enhancing the osteogenic activity of DFCs or inhibiting the eruption of undesirable teeth. Tooth eruption is a complicated process regulated by the dental follicles (DF). Our recent study discovered that tooth eruption was inhibited upon injection of bleomycin into DF. However, the mechanisms were unknown. Human dental follicle cells (hDFCs) were treated by bleomycin or exogenous TGF-β1 or transfected by plasmids loading SMAD7 or shRNA targeting SMAD7, followed by osteogenesis induction assay and signalling analysis. Human fresh DF tissues and Wistar rats were used to further confirm bleomycin function. Bleomycin decreased expression of RUNX2 and osteogenic genes in hDFCs, reducing osteogenic capacity. TGF-β1 expression was up-regulated in bleomycin-treated hDFCs. The effects of exogenous TGF-β1 were similar to those of bleomycin in hDFCs. Additionally, compared to SMAD2/3, SMAD7 expression increased more in bleomycin- or TGF-β1-treated hDFCs. Overexpression of SMAD7 likewise significantly decreased RUNX2 expression and osteogenic capacity of hDFCs. Knockdown of SMAD7 markedly attenuated the inhibitory effects of bleomycin and TGF-β1 on osteogenic capacity and RUNX2 expression of hDFCs. Most importantly, changes in TGF-β1, SMAD7, and RUNX2 expressions were similar in the DF of rats and humans treated with bleomycin. SMAD7 was a negative regulator of osteogenic differentiation in DFCs through suppressing RUNX2 expression. Bleomycin or TGF-β1 inhibited osteogenic differentiation of DFCs via a TGF-β1/SMAD7/RUNX2 pathway. Our findings might be beneficial for enhancing the osteogenic activity of DFCs or inhibiting the eruption of undesirable teeth. |
| Author | Zhao, Ji‐Hong Yang, Ying Li, Zhi‐Zheng Gong, Chu‐Jie Wang, Hai‐Tao Lee, Grace Y. Cai, Yu Wang, Bing Zou, Yan‐Ping Ren, Jian‐Gang |
| Author_xml | – sequence: 1 givenname: Zhi‐Zheng surname: Li fullname: Li, Zhi‐Zheng organization: Wuhan University – sequence: 2 givenname: Hai‐Tao surname: Wang fullname: Wang, Hai‐Tao organization: Wuhan University – sequence: 3 givenname: Grace Y. surname: Lee fullname: Lee, Grace Y. organization: Children's Hospital of Philadelphia – sequence: 4 givenname: Ying surname: Yang fullname: Yang, Ying organization: Wuhan University – sequence: 5 givenname: Yan‐Ping surname: Zou fullname: Zou, Yan‐Ping organization: Wuhan University – sequence: 6 givenname: Bing surname: Wang fullname: Wang, Bing organization: Wuhan University – sequence: 7 givenname: Chu‐Jie surname: Gong fullname: Gong, Chu‐Jie organization: Children's Hospital of Philadelphia – sequence: 8 givenname: Yu surname: Cai fullname: Cai, Yu organization: Wuhan University – sequence: 9 givenname: Jian‐Gang orcidid: 0000-0002-1882-1865 surname: Ren fullname: Ren, Jian‐Gang email: rjg19870708@whu.edu.cn organization: Wuhan University – sequence: 10 givenname: Ji‐Hong surname: Zhao fullname: Zhao, Ji‐Hong email: jhzhao988@whu.edu.cn organization: Wuhan University |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/33068010$$D View this record in MEDLINE/PubMed |
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Tooth eruption is a complicated process regulated by the dental follicles (DF). Our recent study discovered that tooth eruption was... Tooth eruption is a complicated process regulated by the dental follicles (DF). Our recent study discovered that tooth eruption was inhibited upon injection of... Background and PurposeTooth eruption is a complicated process regulated by the dental follicles (DF). Our recent study discovered that tooth eruption was... BACKGROUND AND PURPOSETooth eruption is a complicated process regulated by the dental follicles (DF). Our recent study discovered that tooth eruption was... |
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| SubjectTerms | Bleomycin Cbfa-1 protein dental follicle cell Follicles Osteogenesis Plasmids RUNX2 Signal transduction Smad2 protein SMAD7 Smad7 protein Teeth TGF‐β1 Transforming growth factor-b1 |
| Title | Bleomycin: A novel osteogenesis inhibitor of dental follicle cells via a TGF‐β1/SMAD7/RUNX2 pathway |
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