論文 - 詳細
| RRC ID | 57733 |
|---|---|
| 著者 | Chang SH, Mori D, Kobayashi H, Mori Y, Nakamoto H, Okada K, Taniguchi Y, Sugita S, Yano F, Chung UI, Kim-Kaneyama JR, Yanagita M, Economides A, Canalis E, Chen D, Tanaka S, Saito T. |
| タイトル | Excessive mechanical loading promotes osteoarthritis through the gremlin-1-NF-κB pathway. |
| ジャーナル | Nat Commun |
| Abstract |
Exposure of articular cartilage to excessive mechanical loading is deeply involved in the pathogenesis of osteoarthritis. Here, we identify gremlin-1 as a mechanical loading-inducible factor in chondrocytes, detected at high levels in middle and deep layers of cartilage after cyclic strain or hydrostatic pressure loading. Gremlin-1 activates nuclear factor-κB signalling, leading to subsequent induction of catabolic enzymes. In mice intra-articular administration of gremlin-1 antibody or chondrocyte-specific deletion of Gremlin-1 decelerates osteoarthritis development, while intra-articular administration of recombinant gremlin-1 exacerbates this process. Furthermore, ras-related C3 botulinum toxin substrate 1 activation induced by mechanical loading enhances reactive oxygen species (ROS) production. Amongst ROS-activating transcription factors, RelA/p65 induces Gremlin-1 transcription, which antagonizes induction of anabolic genes such as Sox9, Col2a1, and Acan by bone morphogenetic proteins. Thus, gremlin-1 plays essential roles in cartilage degeneration by excessive mechanical loading. |
| 巻・号 | 10(1) |
| ページ | 1442 |
| 公開日 | 2019-3-29 |
| DOI | 10.1038/s41467-019-09491-5 |
| PII | 10.1038/s41467-019-09491-5 |
| PMID | 30926814 |
| PMC | PMC6441020 |
| MeSH | Anabolic Agents / pharmacology Animals Bone Morphogenetic Proteins / pharmacology Chondrocytes Humans Intercellular Signaling Peptides and Proteins / metabolism* Male Mice, Inbred C57BL Mice, Knockout NF-kappa B / metabolism* Osteoarthritis / metabolism* Osteoarthritis / pathology* Reactive Oxygen Species / metabolism Signal Transduction* Stress, Mechanical Weight-Bearing rac1 GTP-Binding Protein / metabolism |
| IF | 12.121 |
| 引用数 | 18 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 8 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | ATDC5(RCB0565) |