Endothelin-1/endothelin B receptor signalling mediates Prx1+ skeletal stem cells senescence: A driver of osteoporotic bone loss - PubMed
5 hours ago
- #osteoporosis
- #stem cells
- #cellular senescence
- Endothelin-1 (ET-1) and endothelin B receptor (ETBR) signaling drive senescence in Prx1+ skeletal stem cells (SSCs), contributing to osteoporotic bone loss.
- ETBR expression is upregulated in SSCs of aged and ovariectomized (OVX) mice, correlating with bone loss.
- ET-1 overexpression induces SSCs senescence and accelerates bone loss, mimicking aged bone phenotypes.
- In vitro, ET-1 triggers mesenchymal stem cell (MSC) senescence and reactive oxygen species (ROS) accumulation, specifically blocked by ETBR antagonists.
- Transcriptomic analysis shows ET-1/ETBR signaling dysregulates PI3K-AKT and p53 pathways, orchestrating cellular senescence.
- Genetic knockout of ETBR in Prx1+ SSCs or pharmacological inhibition with BQ788 mitigates oxidative stress, reduces senescence, and preserves bone mass in OVX and aged mice.
- ETBR blockade emerges as a promising therapeutic strategy for osteoporosis, targeting the root cause of SSCs exhaustion.