Omics · study · 2026
HDAC4 regulates hASCs osteogenesis and bone regeneration by mediating SMAD4 via histone acetylation
Listed in NCBI GEO
Bone defects in the craniofacial region, such as mandibular critical-sized defects (CSDs), represent a significant clinical challenge due to the limited self-healing capacity and shortcomings of current therapeutic options.
Description
Bone tissue engineering using human adipose-derived stem cells (hASCs) offers a promising alternative. This study investigates the role of histone deacetylase 4 (HDAC4) and its inhibition as a therapeutic strategy in regulating hASCs osteogenic differentiation via histone acetylation.
Using CUT&Tag sequencing, we identified HDAC4-regulated histone acetylation sites that modulate the expression of osteogenesis-related factors, including the key transcription factor SMAD4. HDAC4 knockdown enhanced histone acetylation, promoted SMAD4 expression, and significantly improved osteogenic differentiation of hASCs. These findings were further validated in vivo using calvarial and mandibular defect models in nude mice.
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As an alternative inhibition strategy, the selective HDAC4 inhibitor Tasquinimod (Tasq) was evaluated. At 1 µM, Tasq enhanced hASCs proliferation, promoted histone acetylation, upregulated SMAD4, and stimulated osteogenic differentiation markers (ALP, OSX, COL1A1), mimicking the effects of HDAC4 knockdown. To enable localized delivery, a Tasq-loaded GelMA-F127 composite hydrogel was developed.
This hydrogel exhibited excellent mechanical properties, biocompatibility, and sustained release. Applied to mandibular defects, GelMA-F127-Tasq significantly enhanced bone regeneration. In conclusion, this study elucidates the epigenetic mechanisms of HDAC4 in hASCs osteogenesis and highlights the potential of Tasq-loaded hydrogels as a therapeutic strategy for bone defect repair.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE308nnn/GSE308788 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE308788 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1332721 ncbi.nlm.nih.gov/bioproject/PRJNA1332721 ↗
project · from NCBI GEO
- PubMed 42276061 pubmed.ncbi.nlm.nih.gov/42276061 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Genome binding/occupancy profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- Sequencing 75%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE308788 | 13 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:genome-binding-occupancy-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[modality].local:modality:sequencing | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[organism].NCBITaxon:9606 | 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 |