| First Author | Ji ML | Year | 2023 |
| Journal | Am J Hum Genet | Volume | 110 |
| Issue | 4 | Pages | 606-624 |
| PubMed ID | 36868238 | Mgi Jnum | J:334507 |
| Mgi Id | MGI:7450641 | Doi | 10.1016/j.ajhg.2023.02.011 |
| Citation | Ji ML, et al. (2023) Dynamic chromatin accessibility tuning by the long noncoding RNA ELDR accelerates chondrocyte senescence and osteoarthritis. Am J Hum Genet |
| abstractText | Epigenetic reprogramming plays a critical role in chondrocyte senescence during osteoarthritis (OA) pathology, but the underlying molecular mechanisms remain to be elucidated. Here, using large-scale individual datasets and genetically engineered (Col2a1-CreER(T2);Eldr(flox/flox) and Col2a1-CreER(T2);ROSA26-LSL-Eldr(+/+) knockin) mouse models, we show that a novel transcript of long noncoding RNA ELDR is essential for the development of chondrocyte senescence. ELDR is highly expressed in chondrocytes and cartilage tissues of OA. Mechanistically, exon 4 of ELDR physically mediates a complex consisting of hnRNPL and KAT6A to regulate histone modifications of the promoter region of IHH, thereby activating hedgehog signaling and promoting chondrocyte senescence. Therapeutically, GapmeR-mediated silencing of ELDR in the OA model substantially attenuates chondrocyte senescence and cartilage degradation. Clinically, ELDR knockdown in cartilage explants from OA-affected individuals decreased the expression of senescence markers and catabolic mediators. Taken together, these findings uncover an lncRNA-dependent epigenetic driver in chondrocyte senescence, highlighting that ELDR could be a promising therapeutic avenue for OA. |
