論文 - 詳細
| RRC ID | 82687 |
|---|---|
| 著者 | Arra M, Swarnkar G, Ke K, Otero JE, Ying J, Duan X, Maruyama T, Rai MF, O'Keefe RJ, Mbalaviele G, Shen J, Abu-Amer Y. |
| タイトル | LDHA-mediated ROS generation in chondrocytes is a potential therapeutic target for osteoarthritis. |
| ジャーナル | Nat Commun |
| Abstract |
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-κB 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 IκB-ζ, a critical pro-inflammatory mediator in chondrocytes. IκB-ζ is regulated bi-modally at the stages of transcription and protein degradation. Overall, this work highlights the function of NF-κB 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. |
| 巻・号 | 11(1) |
| ページ | 3427 |
| 公開日 | 2020-7-9 |
| DOI | 10.1038/s41467-020-17242-0 |
| PII | 10.1038/s41467-020-17242-0 |
| PMID | 32647171 |
| PMC | PMC7347613 |
| MeSH | Adaptor Proteins, Signal Transducing / metabolism Aerobiosis Animals Cartilage, Articular / pathology Cells, Cultured Chondrocytes / drug effects Chondrocytes / metabolism* Chondrocytes / pathology Cytoprotection / drug effects Gene Deletion Gene Expression Regulation / drug effects Glycolysis / drug effects Humans Inflammation / metabolism Inflammation / pathology Interleukin-1beta / pharmacology Knee Joint / pathology Lactate Dehydrogenase 5 / metabolism* Menisci, Tibial / surgery Metabolic Networks and Pathways / drug effects Mice, Inbred C57BL Molecular Targeted Therapy* NAD / metabolism NF-kappa B / metabolism Osteoarthritis / drug therapy* Osteoarthritis / genetics Osteoarthritis / pathology Reactive Oxygen Species / metabolism* |
| IF | 12.121 |
| リソース情報 | |
| 実験動物マウス | RBRC06410 |