Omics · study · 2026
Interferon regulatory factor 5 regulates bone remodeling via orchestration of osteoclast lineage-osteoblast coupling
Listed in NCBI GEO
Bone remodeling is orchestrated by the balanced activity of bone-resorbing osteoclasts and bone-forming osteoblasts.
Description
Interferon regulatory factor 5 (IRF5), a member of the IRF family of transcription factors, serves as a critical regulator of macrophage immune-related activity. However, macrophages also serve as the precursor cell of osteoclasts where the role of IRF5 in osteoclast-mediated bone remodeling in vivo remains undefined.
Here, we find that IRF5 exhibits nuclear localization specifically in preosteoclasts during macrophage-osteoclast transition in vitro. In turn, myeloid cell-specific Irf5 conditional knockout (Irf5ΔM/ΔM) mice exhibit a significant osteopenic phenotype. Unexpectedly, osteoclast activity remained unaltered, while osteoblastic bone formation was significantly reduced.
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Interestingly, while conditioned media from wild-type preosteoclasts and osteoclasts increase the osteogenic potential of osteoblastic cells, this stimulatory activity was largely abrogated in conditioned media recovered from Irf5ΔM/ΔM preosteoclasts and osteoclasts. Genome wide analysis further revealed that the Irf5-deficient osteoclast lineage displays major changes in transcriptional programs related to extracellular matrix organization, bone development, and Notch signaling.
Taken together, we have identified IRF5 as a novel osteoimmune transcription factor that coordinates bone remodeling by regulating osteoclast lineage-mediated bone coupling, thus providing novel insights into developing effective preventive and/or therapeutic strategies against metabolic bone diseases.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE297nnn/GSE297530 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE297530 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1265150 ncbi.nlm.nih.gov/bioproject/PRJNA1265150 ↗
project · from NCBI GEO
- PubMed 42331106 pubmed.ncbi.nlm.nih.gov/42331106 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
- Inferred from text
- Genetics 69%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE297530 | 14 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[field].anzsrc:group:3105 | enrichment · NCBI GEO | taxonomy-embedding@1.1.0 | title+keywords+description (69%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[organism].NCBITaxon:10090 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |