Omics · study · 2026
Mitophagy-Replenishment Strategy Targeting the Aberrant Endogenous dsDNA to Enhance Bone Healing Quality in the Elderly
Listed in NCBI GEO
The increased incidence of delayed bone healing in elderly patients is primarily driven by the senescence of bone marrow mesenchymal stem cells (BMSCs), yet the upstream molecular triggers remain incompletely defined.
Description
This study elucidates a novel senescence-driving mechanism: impaired mitophagy and BAX oligomerization-mediated minority mitochondrial outer membrane permeabilization (miMOMP) trigger endogenous dsDNA leakage.
This leakage activates the cGAS–STING signaling axis, establishing a vicious cycle that accelerates BMSC senescence and impairs osteogenesis. To precisely intervene, we developed a targeted composite delivery system (GM-UMPA) comprising AE105-functionalized hollow mesoporous polydopamine (HMPDA) nanoparticles loaded with the mitophagy inducer urolithin A (UA), encapsulated within injectable gelatin methacryloyl (GelMA) microspheres.
Read the rest (2 more)
The hollow mesoporous architecture provides a distinct structural advantage by significantly amplifying drug-loading capacity compared to conventional materials, while surface AE105 peptides enable highly specific uPAR-mediated endocytosis into senescent cells. Crucially, the weakly basic HMPDA framework exhibits pH-responsive drug release characteristics, triggering rapid intracellular UA liberation specifically within the acidic microenvironment of senescent BMSCs.
Validated using an in vitro BMSC replicative senescence model and an in vivo critical-sized femoral condyle defect model in aged rats, this hierarchical platform successfully cleared damaged mitochondria, suppressed senescence-associated secretory phenotypes (SASP), and substantially accelerated high-quality bone regeneration. Ultimately, this mitophagy-replenishment strategy offers a structurally innovative, responsive nanomedicine paradigm for treating age-related bone healing disorders.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE339nnn/GSE339437 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE339437 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1498668 ncbi.nlm.nih.gov/bioproject/PRJNA1498668 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Rattus norvegicus
- From keywords
- Life Sciences
Provenance · 1 source records, 7 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE339437 | 15 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:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[organism].NCBITaxon:10116 | 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 |