Inhibiting cGAS-STING to Preserve Mitochondrial-Nuclear Communication and Stemness in Young Tendon Stem Cells: A Hydrogel Strategy against Age-Related Tendinopathy - PubMed
3 hours ago
- #tendinopathy
- #hydrogel-therapy
- #stem-cells
- Age-related tendinopathy is common in the elderly and linked to low cellular density and poor blood supply in tendons.
- Key pathological features include accumulation of senescent tendon-derived stem cells (TDSCs), decrease in young TDSCs, and inflammatory imbalance caused by ROS.
- Impaired mitochondria-nucleus communication is a central mechanism in disease progression.
- A ROS-responsive dual-targeted hydrogel (P/H@Lipo) loaded with selenium nanocatalysts (HPSe) and STING inhibitor H-151 was developed.
- The hydrogel releases L-Lipo@H-151 in response to ROS, targeting TDSCs to inhibit the cGAS-STING pathway.
- HPSe reduces mtDNA leakage and cGAMP production, strengthening the blockade of the cGAS-STING pathway.
- This process maintains mitochondrial-nuclear communication and preserves stemness in young TDSCs by preventing senescence.
- HPSe boosts self-renewal and tendinogenic differentiation in young TDSCs by inhibiting the Hippo signaling pathway.
- The study presents a novel therapeutic paradigm targeting mitochondrial-nuclear communication to combat age-related tendinopathy.