TLE4 Is a Critical Mediator of Osteoblast and Runx2-Dependent Bone Development

Thomas H. Shin; Thomas H. Shin; Evangelos Theodorou; Carl Holland; Rae’e Yamin; Cathleen L. Raggio; Philip F. Giampietro; David A. Sweetser

doi:10.3389/fcell.2021.671029

Frontiers in Cell and Developmental Biology (Aug 2021)

TLE4 Is a Critical Mediator of Osteoblast and Runx2-Dependent Bone Development

Thomas H. Shin,
Thomas H. Shin,
Evangelos Theodorou,
Carl Holland,
Rae’e Yamin,
Cathleen L. Raggio,
Philip F. Giampietro,
David A. Sweetser

Affiliations

Thomas H. Shin: Department of Pediatrics, Center of Genomic Medicine, Divisions of Pediatric Hematology/Oncology and Medical Genetics, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
Thomas H. Shin: Department of Molecular and Translational Medicine, Boston University School of Medicine, Boston, MA, United States
Evangelos Theodorou: Department of Pediatrics, Center of Genomic Medicine, Divisions of Pediatric Hematology/Oncology and Medical Genetics, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
Carl Holland: Department of Pediatrics, Center of Genomic Medicine, Divisions of Pediatric Hematology/Oncology and Medical Genetics, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
Rae’e Yamin: Department of Pediatrics, Center of Genomic Medicine, Divisions of Pediatric Hematology/Oncology and Medical Genetics, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
Cathleen L. Raggio: Department of Pediatric Orthopedics, Hospital for Special Surgery, New York, NY, United States
Philip F. Giampietro: Department of Pediatrics, University of Illinois, Chicago, IL, United States
David A. Sweetser: Department of Pediatrics, Center of Genomic Medicine, Divisions of Pediatric Hematology/Oncology and Medical Genetics, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States

DOI: https://doi.org/10.3389/fcell.2021.671029
Journal volume & issue: Vol. 9

Abstract

Read online

Healthy bone homeostasis hinges upon a delicate balance and regulation of multiple processes that contribute to bone development and metabolism. While examining hematopoietic regulation by Tle4, we have uncovered a previously unappreciated role of Tle4 on bone calcification using a novel Tle4 null mouse model. Given the significance of osteoblasts in both hematopoiesis and bone development, this study investigated how loss of Tle4 affects osteoblast function. We used dynamic bone formation parameters and microCT to characterize the adverse effects of Tle4 loss on bone development. We further demonstrated loss of Tle4 impacts expression of several key osteoblastogenic genes, including Runx2, Oc, and Ap, pointing toward a potential novel mechanism for Tle4-dependent regulation of mammalian bone development in collaboration with the RUNX family members.

Published in Frontiers in Cell and Developmental Biology

ISSN: 2296-634X (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Science: Biology (General)
Website: https://www.frontiersin.org/journals/cell-and-developmental-biology

About the journal

Abstract

Keywords