ArticleStem cell reports2018
Translational Control of Sox9 RNA by mTORC1 Contributes to Skeletogenesis.
Article in Stem cell reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 28 citations in OpenAlex.
- Altered Sox9 and FGF signaling gene expression in Aga2 OI mice negatively affects linear growth.JCI insight · 2023Article
- Localized heterochrony integrates overgrowth potential of oncogenic clones.Disease models & mechanisms · 2023Article
- Look who's TORking: mTOR-mediated integration of cell status and external signals during limb development and endochondral bone growth.Frontiers in cell and developmental biology · 2023Review
- Cooperative effects of oocytes and estrogen on the forkhead box L2 expression in mural granulosa cells in mice.Scientific reports · 2022Article
- The role of CDK8 in mesenchymal stem cells in controlling osteoclastogenesis and bone homeostasis.Stem cell reports · 2022Article
- Nsun4 and Mettl3 mediated translational reprogramming of Sox9 promotes BMSC chondrogenic differentiation.Communications biology · 2022Article
- mRNA Translation Is Dynamically Regulated to Instruct Stem Cell Fate.Frontiers in molecular biosciences · 2022Review
- Human ESC-sEVs alleviate age-related bone loss by rejuvenating senescent bone marrow-derived mesenchymal stem cells.Journal of extracellular vesicles · 2020Article
- GCN5 acetylation is required for craniofacial chondrocyte maturation.Developmental biology · 2020Article
- Hypoxia affects Slc7a5 expression through HIF-2α in differentiated neuronal cells.FEBS open bio · 2019Article
- Cartilage Induction from Mouse Mesenchymal Stem Cells in High-density Micromass Culture.Bio-protocol · 2019Article
- mTORC1 Activation in Osteoclasts Prevents Bone Loss in a Mouse Model of Osteoporosis.Frontiers in pharmacology · 2019Article
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Authors and funding
16 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mechanistic/mammalian target of rapamycin complex 1 (mTORC1) regulates cellular function in various cell types. Although the role of mTORC1 in skeletogenesis has been investigated previously, here we show a critical role of mTORC1/4E-BPs/SOX9 axis in regulating skeletogenesis through its expression in undifferentiated mesenchymal cells. Inactivation of Raptor, a component of mTORC1, in limb buds before mesenchymal condensations resulted in a marked loss of both cartilage and bone. Mechanistically, we demonstrated that mTORC1 selectively controls the RNA translation of Sox9, which harbors a 5' terminal oligopyrimidine tract motif, via inhibition of the 4E-BPs. Indeed, introduction of Sox9 or a knockdown of 4E-BP1/2 in undifferentiated mesenchymal cells markedly rescued the deficiency of the condensation observed in Raptor-deficient mice. Furthermore, introduction of the Sox9 transgene rescued phenotypes of deficient skeletal growth in Raptor-deficient mice. These findings highlight a critical role of mTORC1 in mammalian skeletogenesis, at least in part, through translational control of Sox9 RNA.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.