| Expression pattern: |
DN |
| Associated gene: |
Ago2, SIRT3, IDH2, MnSOD |
| Associated microRNA: |
miR-206 |
| Biological function: |
circHIPK2 protects against OA-associated chondrocyte injury by mitigating apoptosis and metabolic stress, reducing glycolytic activation, restoring mitochondrial respiration and ATP production, improving mitochondrial homeostasis, attenuating cartilage degradation, and alleviating OA-induced nociceptive behaviors. |
| Molecular mechanism: |
circHIPK2 acts as a ceRNA that directly sequesters miR-206 through Ago2-dependent interactions, relieving miR-206-mediated suppression of SIRT3 and promoting SIRT3-dependent mitochondrial deacetylation programs involving IDH2 and MnSOD. |
| Biological pathway or process: |
ceRNA regulation (other); glycolysis (inhibits); oxidative phosphorylation (promotes); mitochondrial function (promotes); apoptosis (inhibits); drug resistance (other); other pathway/process (inhibits) |
| Detected method: |
Q
|
| Validation methods: |
RT-qPCR; Clinical Sample Validation; Transfection; RIP (RNA Immunoprecipitation); RNA Pull-Down; Luciferase Reporter Assay; MTT; Annexin V/PI Flow Cytometry; ELISA; Western Blot; In Vivo Animal Model; Bioinformatics Analysis |
| Clinical significance: |
circHIPK2 is reduced in OA patient chondrocytes, correlates positively with SIRT3 and negatively with miR-206, and lower circHIPK2 expression is associated with greater OA structural severity. |
| Description: |
circHIPK2 is downregulated in OA chondrocytes and functions as a protective circRNA in OA. It sponges miR-206 to preserve SIRT3 expression and activity, thereby restoring mitochondrial homeostasis, oxidative phosphorylation, ATP production, and antioxidant function while suppressing glycolytic stress and apoptosis. In vivo AAV-mediated circHIPK2 delivery alleviates OA pain behaviors and cartilage degeneration in MIA and DMM rat models. |
| Confidence score: |
0.7289 |