| First Author | Kim P | Year | 2022 |
| Journal | Nat Commun | Volume | 13 |
| Issue | 1 | Pages | 3960 |
| PubMed ID | 35803931 | Mgi Jnum | J:326767 |
| Mgi Id | MGI:7313530 | Doi | 10.1038/s41467-022-31697-3 |
| Citation | Kim P, et al. (2022) Mast4 determines the cell fate of MSCs for bone and cartilage development. Nat Commun 13(1):3960 |
| abstractText | 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-beta and Wnt signal transduction in regulating chondro-osteogenic differentiation of MSCs. Suppression of Mast4 by TGF-beta1 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-3beta and subsequent Smurf1 recruitment, promoted beta-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. |
