Immunorthodontics: in vivo gene expression of orthodontic tooth movement

Yehuda Klein; Omer Fleissig; David Polak; Yechezkel Barenholz; Ofer Mandelboim; Stella Chaushu

doi:10.1038/s41598-020-65089-8

Immunorthodontics: in vivo gene expression of orthodontic tooth movement

Yehuda Klein, Omer Fleissig^*, David Polak, Yechezkel Barenholz, Ofer Mandelboim, Stella Chaushu

^*Corresponding author for this work

Department of Immunology and Cancer Research

Research output: Contribution to journal › Article › peer-review

25 Scopus citations

Abstract

Orthodontic tooth movement (OTM) is a “sterile” inflammatory process. The present study aimed to reveal the underlying biological mechanisms, by studying the force associated-gene expression changes, in a time-dependent manner. Ni-Ti springs were set to move the upper 1^st-molar in C57BL/6 mice. OTM was measured by μCT. Total-RNA was extracted from tissue blocks at 1,3,7 and 14-days post force application, and from two control groups: naïve and inactivated spring. Gene-expression profiles were generated by next-generation-RNA-sequencing. Gene Set Enrichment Analysis, K-means algorithm and Ingenuity pathway analysis were used for data interpretation. Genes of interest were validated with qRT-PCR. A total of 3075 differentially expressed genes (DEGs) were identified, with the greatest number at day 3. Two distinct clusters patterns were recognized: those in which DEGs peaked in the first days and declined thereafter (tissue degradation, phagocytosis, leukocyte extravasation, innate and adaptive immune system responses), and those in which DEGs were initially down-regulated and increased at day 14 (cell proliferation and migration, cytoskeletal rearrangement, tissue homeostasis, angiogenesis). The uncovering of novel innate and adaptive immune processes in OTM led us to propose a new term “Immunorthodontics”. This genomic data can serve as a platform for OTM modulation future approaches.

Original language	American English
Article number	8172
Journal	Scientific Reports
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41598-020-65089-8
State	Published - 1 Dec 2020

Bibliographical note

Funding Information:
This work was supported by the Israel Science Foundation and the Cabacoff Foundation. The authors also wish to acknowledge Dr. Abedelmajeed Nasereddin (Genomic Applications Laboratory, The Core Research Facility, The Faculty of Medicine - Ein Kerem, The Hebrew University of Jerusalem, Israel) for his help with the mRNA Library preparation and to Dr. Yuval Nevo, Dr. Shrona Elgavish and Dr. Hadar Benyamini (Bioinformatics Unit of the I-CORE Computation Center, The Hebrew University and Hadassah Medical Center, Jerusalem, Israel) for their help with the bioinformatic analysis.

Publisher Copyright:
© 2020, The Author(s).

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title = "Immunorthodontics: in vivo gene expression of orthodontic tooth movement",

abstract = "Orthodontic tooth movement (OTM) is a “sterile” inflammatory process. The present study aimed to reveal the underlying biological mechanisms, by studying the force associated-gene expression changes, in a time-dependent manner. Ni-Ti springs were set to move the upper 1st-molar in C57BL/6 mice. OTM was measured by μCT. Total-RNA was extracted from tissue blocks at 1,3,7 and 14-days post force application, and from two control groups: na{\"i}ve and inactivated spring. Gene-expression profiles were generated by next-generation-RNA-sequencing. Gene Set Enrichment Analysis, K-means algorithm and Ingenuity pathway analysis were used for data interpretation. Genes of interest were validated with qRT-PCR. A total of 3075 differentially expressed genes (DEGs) were identified, with the greatest number at day 3. Two distinct clusters patterns were recognized: those in which DEGs peaked in the first days and declined thereafter (tissue degradation, phagocytosis, leukocyte extravasation, innate and adaptive immune system responses), and those in which DEGs were initially down-regulated and increased at day 14 (cell proliferation and migration, cytoskeletal rearrangement, tissue homeostasis, angiogenesis). The uncovering of novel innate and adaptive immune processes in OTM led us to propose a new term “Immunorthodontics”. This genomic data can serve as a platform for OTM modulation future approaches.",

author = "Yehuda Klein and Omer Fleissig and David Polak and Yechezkel Barenholz and Ofer Mandelboim and Stella Chaushu",

note = "Funding Information: This work was supported by the Israel Science Foundation and the Cabacoff Foundation. The authors also wish to acknowledge Dr. Abedelmajeed Nasereddin (Genomic Applications Laboratory, The Core Research Facility, The Faculty of Medicine - Ein Kerem, The Hebrew University of Jerusalem, Israel) for his help with the mRNA Library preparation and to Dr. Yuval Nevo, Dr. Shrona Elgavish and Dr. Hadar Benyamini (Bioinformatics Unit of the I-CORE Computation Center, The Hebrew University and Hadassah Medical Center, Jerusalem, Israel) for their help with the bioinformatic analysis. Publisher Copyright: {\textcopyright} 2020, The Author(s).",

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AU - Mandelboim, Ofer

AU - Chaushu, Stella

N1 - Funding Information: This work was supported by the Israel Science Foundation and the Cabacoff Foundation. The authors also wish to acknowledge Dr. Abedelmajeed Nasereddin (Genomic Applications Laboratory, The Core Research Facility, The Faculty of Medicine - Ein Kerem, The Hebrew University of Jerusalem, Israel) for his help with the mRNA Library preparation and to Dr. Yuval Nevo, Dr. Shrona Elgavish and Dr. Hadar Benyamini (Bioinformatics Unit of the I-CORE Computation Center, The Hebrew University and Hadassah Medical Center, Jerusalem, Israel) for their help with the bioinformatic analysis. Publisher Copyright: © 2020, The Author(s).

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N2 - Orthodontic tooth movement (OTM) is a “sterile” inflammatory process. The present study aimed to reveal the underlying biological mechanisms, by studying the force associated-gene expression changes, in a time-dependent manner. Ni-Ti springs were set to move the upper 1st-molar in C57BL/6 mice. OTM was measured by μCT. Total-RNA was extracted from tissue blocks at 1,3,7 and 14-days post force application, and from two control groups: naïve and inactivated spring. Gene-expression profiles were generated by next-generation-RNA-sequencing. Gene Set Enrichment Analysis, K-means algorithm and Ingenuity pathway analysis were used for data interpretation. Genes of interest were validated with qRT-PCR. A total of 3075 differentially expressed genes (DEGs) were identified, with the greatest number at day 3. Two distinct clusters patterns were recognized: those in which DEGs peaked in the first days and declined thereafter (tissue degradation, phagocytosis, leukocyte extravasation, innate and adaptive immune system responses), and those in which DEGs were initially down-regulated and increased at day 14 (cell proliferation and migration, cytoskeletal rearrangement, tissue homeostasis, angiogenesis). The uncovering of novel innate and adaptive immune processes in OTM led us to propose a new term “Immunorthodontics”. This genomic data can serve as a platform for OTM modulation future approaches.

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Immunorthodontics: in vivo gene expression of orthodontic tooth movement

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