論文 - 詳細
| RRC ID | 83168 |
|---|---|
| 著者 | Miyahara J, Omata Y, Chijimatsu R, Okada H, Ishikura H, Higuchi J, Tachibana N, Nagata K, Tani S, Kono K, Kawaguchi K, Yamagami R, Inui H, Taketomi S, Iwanaga Y, Terashima A, Yano F, Seki M, Suzuki Y, Baron R, Tanaka S, Saito T. |
| タイトル | CD34hi subset of synovial fibroblasts contributes to fibrotic phenotype of human knee osteoarthritis. |
| ジャーナル | JCI Insight |
| Abstract |
Osteoarthritis (OA) shows various clinical manifestations depending on the status of its joint components. We aimed to identify the synovial cell subsets responsible for OA pathophysiology by comprehensive analyses of human synovium samples in single-cell resolution. Two distinct OA synovial tissue groups were classified by gene expression profiles in RNA-Seq: inflammatory and fibrotic. The inflammatory group exhibited high expression of inflammatory cytokines, histologically inflammatory infiltrate, and a more severe pain score. The fibrotic group showed higher expression of fibroblast growth factor (FGFs) and bone morphogenetic proteins (BMPs), showed histologically perivascular fibrosis, and showed a lower pain score. In single-cell RNA-Seq (scRNA-Seq) of synovial cells, MERTKloCD206lo macrophages and CD34hi fibroblasts were associated with the inflammatory and fibrotic groups, respectively. Among the 3 fibroblast subsets, CD34loTHY1lo and CD34loTHY1hi fibroblasts were influenced by synovial immune cells, whereas CD34hi fibroblasts were influenced by mural and endothelial cells. Particularly, in CD34hi fibroblast subsets, CD34hiCD70hi fibroblasts promoted proliferation of Tregs, potentially suppressing synovitis and protecting articular cartilage. Elucidation of the mechanisms underlying the regulation of these synovial cell subsets may lead to novel strategies for OA therapeutics. |
| 巻・号 | 10(2) |
| 公開日 | 2025-1-23 |
| DOI | 10.1172/jci.insight.183690 |
| PII | 183690 |
| PMID | 39846253 |
| PMC | PMC11790023 |
| MeSH | Aged Antigens, CD34* / metabolism Female Fibroblasts* / metabolism Fibroblasts* / pathology Fibrosis* Humans Male Middle Aged Osteoarthritis, Knee* / genetics Osteoarthritis, Knee* / metabolism Osteoarthritis, Knee* / pathology Phenotype Synovial Membrane* / metabolism Synovial Membrane* / pathology |
| IF | 6.205 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 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 | MRC-5 (RCB2833) |