Clonal Hematopoiesis Driven by Mutated DNMT3A Promotes Inflammatory Bone Loss

Authors

Hui Wang
Kimon Divaris
Bohu Pan
Xiaofei Li
Jong-Hyung Lim
Gundappa Saha
Marko Barovic
Danai Giannakou
Jonathan M Korostoff
Yu Bing
Souvik Sen
Kevin Moss
Di Wu
James D Beck
Christie M Ballantyne
Pradeep Natarajan
Kari E North
Mihai G Netea
Triantafyllos Chavakis
George Hajishengallis

Publication Date

7-11-2024

Journal

Cell

Abstract

Clonal hematopoiesis of indeterminate potential (CHIP) arises from aging-associated acquired mutations in hematopoietic progenitors, which display clonal expansion and produce phenotypically altered leukocytes. We associated CHIP-DNMT3A mutations with a higher prevalence of periodontitis and gingival inflammation among 4,946 community-dwelling adults. To model DNMT3A-driven CHIP, we used mice with the heterozygous loss-of-function mutation R878H, equivalent to the human hotspot mutation R882H. Partial transplantation with Dnmt3a

Keywords

DNA Methyltransferase 3A, Animals, DNA (Cytosine-5-)-Methyltransferases, Mice, Clonal Hematopoiesis, Humans, Periodontitis, Mutation, Male, Female, Inflammation, Osteoclasts, Mice, Inbred C57BL, Adult, Interleukin-17, T-Lymphocytes, Regulatory, Hematopoiesis, Osteogenesis, Hematopoietic Stem Cells, Bone Resorption, Middle Aged

DOI

10.1016/j.cell.2024.05.003

PMID

38838669

PMCID

PMC11246233

PubMedCentral® Posted Date

7-14-2024

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes