RRC ID 74469
Author Tanaka T, Takahashi A, Kobayashi Y, Saito M, Xiaolong S, Jingquan C, Ito Y, Kato T, Ochi H, Sato S, Yoshii T, Okawa A, Carlsson P, Inose H.
Title Foxf2 represses bone formation via Wnt2b/β-catenin signaling.
Journal Exp Mol Med
Abstract Differentiation of mesenchymal stem cells (MSCs) into osteoblasts is a critical process for proper skeletal development and acquisition/maintenance of bone mass. However, since this regulatory mechanism has not yet been fully elucidated, the treatment of severe osteoporosis and fractures is a challenge. Here, through a comprehensive analysis of gene expression during the differentiation of MSCs into osteoblasts, we show that the forkhead transcription factor Foxf2 is a crucial regulator of this process. Foxf2 expression transiently increased during MSC osteoblastic differentiation. Overexpression of Foxf2 in MSCs inhibited osteoblastic differentiation, and conversely, knockdown of Foxf2 expression promoted this process. Osteoprogenitor-specific Foxf2 knockout mice developed a high bone mass phenotype due to increased bone formation. RNA-seq analysis and molecular experiments revealed that Foxf2 regulation of bone formation is mediated by Wnt2b. Knockdown of Foxf2 in mouse femurs enhanced bone regeneration in vivo. FOXF2 expression was correlated with hip bone mineral density in postmenopausal women with low bone mass. Finally, inhibition of FOXF2 promoted osteoblastic differentiation of human MSCs. This study uncovers a critical role of Foxf2 in the differentiation of MSCs into osteoblasts and provides insight into the pathogenesis associated with bone-related diseases such as osteoporosis and nonunion after fracture.
Volume 54(6)
Pages 753-764
Published 2022-6-1
DOI 10.1038/s12276-022-00779-z
PII 10.1038/s12276-022-00779-z
PMID 35668101
PMC PMC9256714
MeSH Animals Cell Differentiation / genetics Female Forkhead Transcription Factors / genetics Forkhead Transcription Factors / metabolism Glycoproteins / metabolism Mice Mice, Knockout Osteoblasts / metabolism Osteogenesis / genetics Osteoporosis* / genetics Wnt Proteins / metabolism Wnt Signaling Pathway* beta Catenin / genetics beta Catenin / metabolism
IF 5.418
Human and Animal Cells ST2 (RCB0224)