Osteoclastogenesis Responds to STING Inhibition in a Non-Monotonic Manner - PubMed
4 hours ago
- #osteoporosis
- #osteoclastogenesis
- #STING
- STING temporally regulates osteoclast differentiation without affecting osteoblast-mediated bone homeostasis.
- Early STING inhibition significantly increases bone mass in OVX mice, but efficacy decreases in later stages, with terminal stage intervention worsening bone loss.
- Osteoblast-specific Sting knockout mice show no change in bone mass in static or OVX conditions.
- STING downstream pathways (NF-κB and IFN) bidirectionally control osteoclast differentiation: NF-κB drives cell commitment, while IFN inhibits multinuclear maturation.
- Stage-specific activation of NF-κB and IFN pathways was confirmed during human and murine osteoclastogenesis.
- The study highlights a critical early therapeutic window for STING inhibition in osteoporosis treatment.