PUBLICATION
Integrative analysis reveals synergistic regulation of Sp7 by BRD9 and Wnt/β-catenin signaling during osteogenic differentiation
- Authors
- Wu, L., Wang, L., Zhuang, Y., Luo, Y., Zhu, Q., Maimaitizunong, M., Wang, Y., Cheng, Z., Li, Y., Sheng, X., Li, M., Luo, Q., Jiang, X., Lei, S., Lin, X., Zhong, Y., Ren, W.
- ID
- ZDB-PUB-251202-9
- Date
- 2025
- Source
- Communications biology : (Journal)
- Registered Authors
- Zhong, Yingbin
- Keywords
- none
- MeSH Terms
-
- Animals
- Bromodomain Containing Proteins
- Cell Differentiation*/genetics
- DNA-Binding Proteins*/genetics
- DNA-Binding Proteins*/metabolism
- Humans
- Mice
- Osteoblasts/cytology
- Osteoblasts/metabolism
- Osteogenesis*/genetics
- Osteoporosis/genetics
- Osteoporosis/metabolism
- Sp7 Transcription Factor*/genetics
- Sp7 Transcription Factor*/metabolism
- Transcription Factors*/genetics
- Transcription Factors*/metabolism
- Wnt Signaling Pathway*
- Zebrafish
- PubMed
- 41326797 Full text @ Commun Biol
Citation
Wu, L., Wang, L., Zhuang, Y., Luo, Y., Zhu, Q., Maimaitizunong, M., Wang, Y., Cheng, Z., Li, Y., Sheng, X., Li, M., Luo, Q., Jiang, X., Lei, S., Lin, X., Zhong, Y., Ren, W. (2025) Integrative analysis reveals synergistic regulation of Sp7 by BRD9 and Wnt/β-catenin signaling during osteogenic differentiation. Communications biology. :.
Abstract
Osteoporosis is a complex skeletal disorder characterized by low bone mineral density (BMD). Compared with classical epigenetic modifications, such as DNA methylation and histone modifications, the participation of chromatin-remodeling complexes in osteoporosis remains less explored. To identify chromatin remodeling factors causally associated with bone mineral density (BMD), here we conducted a systematic analysis of 87 genes encoding components of four major chromatin-remodeling complexes using Summary-data-based Mendelian randomization (SMR) analysis. Candidate chromatin-remodeling factors were further cross-referenced with publicly available skeletal phenotyping data from the International Mouse Phenotyping Consortium (IMPC) database. Functional validation revealed that non-canonical BAF (ncBAF) subunit BRD9 is essential for osteoblast differentiation using both in vitro cell culture and in vivo zebrafish models. RNA-Sequencing (RNA-Seq) demonstrated that BRD9 orchestrates osteogenic differentiation by modulating Wnt/β-catenin signaling activity. Mechanistically, the osteogenic master transcription factor Sp7 was identified as a direct transcriptional target of BRD9, whose expression is coordinately controlled through the synergistic interplay between BRD9 and Wnt/β-catenin signaling during osteogenesis. Collectively, this study established a comprehensive framework for identifying causal genes implicated in osteoporosis and elucidated the previously unrecognized regulatory role of BRD9 in osteogenesis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping