Differential Gene Expression Involved in Bone Turnover of Mice Expressing Constitutively Active TGFβ Receptor Type I.

TitleDifferential Gene Expression Involved in Bone Turnover of Mice Expressing Constitutively Active TGFβ Receptor Type I.
Publication TypeJournal Article
Year of Publication2024
AuthorsMyint O, Sakunrangsit N, Pholtaisong J, Toejing P, Pho-On P, Leelahavanichkul A, Sridurongrit S, Aporntewan C, Greenblatt MB, Lotinun S
JournalInt J Mol Sci
Volume25
Issue11
Date Published2024 May 27
ISSN1422-0067
KeywordsAnimals, Bone Remodeling, Cell Differentiation, Gene Expression Profiling, Gene Expression Regulation, Histone Deacetylases, Mice, Osteoblasts, Osteoclasts, Receptor, Transforming Growth Factor-beta Type I
Abstract

Transforming growth factor beta (TGF-β) is ubiquitously found in bone and plays a key role in bone turnover. Mice expressing constitutively active TGF-β receptor type I (Mx1;TβRICA mice) are osteopenic. Here, we identified the candidate genes involved in bone turnover in Mx1;TβRICA mice using RNA sequencing analysis. A total of 285 genes, including 87 upregulated and 198 downregulated genes, were differentially expressed. According to the KEGG analysis, some genes were involved in osteoclast differentiation (Fcgr4, Lilrb4a), B cell receptor signaling (Cd72, Lilrb4a), and neutrophil extracellular trap formation (Hdac7, Padi4). Lilrb4 is related to osteoclast inhibition protein, whereas Hdac7 is a Runx2 corepressor that regulates osteoblast differentiation. Silencing Lilrb4 increased the number of osteoclasts and osteoclast marker genes. The knocking down of Hdac7 increased alkaline phosphatase activity, mineralization, and osteoblast marker genes. Therefore, our present study may provide an innovative idea for potential therapeutic targets and pathways in TβRI-associated bone loss.

DOI10.3390/ijms25115829
Alternate JournalInt J Mol Sci
PubMed ID38892016
PubMed Central IDPMC11173332
Grant ListHEA663200063 and DRF67_008 / / Thailand Science Research and Innovation Fund, Faculty Research Grant, Faculty of Dentistry and the Second Century Fund (C2F), Chulalongkorn University. /
Related Faculty: 
Matthew B. Greenblatt, M.D., Ph.D.

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