論文 - 詳細
| RRC ID | 72010 |
|---|---|
| 著者 | Kim P, Park J, Lee DJ, Mizuno S, Shinohara M, Hong CP, Jeong Y, Yun R, Park H, Park S, Yang KM, Lee MJ, Jang SP, Kim HY, Lee SJ, Song SU, Park KS, Tanaka M, Ohshima H, Cho JW, Sugiyama F, Takahashi S, Jung HS, Kim SJ. |
| タイトル | Mast4 determines the cell fate of MSCs for bone and cartilage development. |
| ジャーナル | Nat Commun |
| Abstract |
Mesenchymal stromal cells (MSCs) differentiation into different lineages is precisely controlled by signaling pathways. Given that protein kinases play a crucial role in signal transduction, here we show that Microtubule Associated Serine/Threonine Kinase Family Member 4 (Mast4) serves as an important mediator of TGF-β and Wnt signal transduction in regulating chondro-osteogenic differentiation of MSCs. Suppression of Mast4 by TGF-β1 led to increased Sox9 stability by blocking Mast4-induced Sox9 serine 494 phosphorylation and subsequent proteasomal degradation, ultimately enhancing chondrogenesis of MSCs. On the other hand, Mast4 protein, which stability was enhanced by Wnt-mediated inhibition of GSK-3β and subsequent Smurf1 recruitment, promoted β-catenin nuclear localization and Runx2 activity, increasing osteogenesis of MSCs. Consistently, Mast4-/- mice demonstrated excessive cartilage synthesis, while exhibiting osteoporotic phenotype. Interestingly, Mast4 depletion in MSCs facilitated cartilage formation and regeneration in vivo. Altogether, our findings uncover essential roles of Mast4 in determining the fate of MSC development into cartilage or bone. |
| 巻・号 | 13(1) |
| ページ | 3960 |
| 公開日 | 2022-7-8 |
| DOI | 10.1038/s41467-022-31697-3 |
| PII | 10.1038/s41467-022-31697-3 |
| PMID | 35803931 |
| PMC | PMC9270402 |
| MeSH | Animals Bone and Bones* / cytology Bone and Bones* / metabolism Cartilage* / cytology Cartilage* / metabolism Cell Differentiation / genetics Chondrogenesis / genetics Female Mesenchymal Stem Cells* / cytology Mesenchymal Stem Cells* / metabolism Mice Mice, Inbred C57BL Mice, Knockout Microtubule-Associated Proteins* / genetics Osteogenesis / genetics Protein Serine-Threonine Kinases* / genetics Transforming Growth Factor beta / metabolism Wnt Signaling Pathway |
| IF | 12.121 |
| 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 | 5 |
| 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) |