| First Author | Arra M | Year | 2020 |
| Journal | Nat Commun | Volume | 11 |
| Issue | 1 | Pages | 3427 |
| PubMed ID | 32647171 | Mgi Jnum | J:292290 |
| Mgi Id | MGI:6447758 | Doi | 10.1038/s41467-020-17242-0 |
| Citation | Arra M, et al. (2020) LDHA-mediated ROS generation in chondrocytes is a potential therapeutic target for osteoarthritis. Nat Commun 11(1):3427 |
| abstractText | The contribution of inflammation to the chronic joint disease osteoarthritis (OA) is unclear, and this lack of clarity is detrimental to efforts to identify therapeutic targets. Here we show that chondrocytes under inflammatory conditions undergo a metabolic shift that is regulated by NF-kappaB activation, leading to reprogramming of cell metabolism towards glycolysis and lactate dehydrogenase A (LDHA). Inflammation and metabolism can reciprocally modulate each other to regulate cartilage degradation. LDHA binds to NADH and promotes reactive oxygen species (ROS) to induce catabolic changes through stabilization of IkappaB-zeta, a critical pro-inflammatory mediator in chondrocytes. IkappaB-zeta is regulated bi-modally at the stages of transcription and protein degradation. Overall, this work highlights the function of NF-kappaB activity in the OA joint as well as a ROS promoting function for LDHA and identifies LDHA as a potential therapeutic target for OA treatment. |
