ArticleThe Journal of experimental medicine2015
mTOR inhibition rescues osteopenia in mice with systemic sclerosis.
Article in The Journal of experimental medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
53 citing papers in PubMed, 96 citations in OpenAlex.
- Prolonged TNF-α stimulation induces a PD-1-associated exhaustion-like phenotype in mesenchymal stromal cells.Frontiers in cell and developmental biology · 2026Article
- The genetics of hyper IgE syndromes.Frontiers in immunology · 2025Review
- Modulating Proliferation, Migration and Differentiation of Mesenchymal Stem Cells Using Interleukins.Current stem cell research & therapy · 2025Review
- MicroRNA-19b exacerbates systemic sclerosis through promoting Th9 cells.Cell reports · 2024Article
- Scaffold Application for Bone Regeneration with Stem Cells in Dentistry: Literature Review.Cells · 2024Review
- Unveiling the role of hypoxia-inducible factor 2alpha in osteoporosis: Implications for bone health.World journal of stem cells · 2024Article
- Research progress on the regulatory mechanism of integrin-mediated mechanical stress in cells involved in bone metabolism.Journal of cellular and molecular medicine · 2024Review
- ERBIN and phosphoglucomutase 3 deficiency.Current opinion in immunology · 2023Review
- Identification of key ferroptosis-related biomarkers in steroid-induced osteonecrosis of the femoral head based on machine learning.Journal of orthopaedic surgery and research · 2023Article
- Mesenchymal stem cells: Emerging concepts and recent advances in their roles in organismal homeostasis and therapy.Frontiers in cellular and infection microbiology · 2023Review
- The extracellular matrix glycoprotein fibrillin-1 in health and disease.Frontiers in cell and developmental biology · 2023Review
- Bone regeneration strategies based on organelle homeostasis of mesenchymal stem cells.Frontiers in endocrinology · 2023Review
- [Progress of pathogenesis and genetics of alcohol-induced osteonecrosis of femoral head].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2022Review
- Activation of Functional Somatic Stem Cells Promotes Endogenous Tissue Regeneration.Journal of dental research · 2022Article
- Metabolic Reconfiguration Activates Stemness and Immunomodulation of PDLSCs.International journal of molecular sciences · 2022Article
- Kartogenin Improves Osteogenesis of Bone Marrow Mesenchymal Stem Cells via Autophagy.Stem cells international · 2022Article
- The crosstalk between MYC and mTORC1 during osteoclastogenesis.Frontiers in cell and developmental biology · 2022Article
- The Roles of Noncoding RNAs in Systemic Sclerosis.Frontiers in immunology · 2022Review
- Article
- MicroRNA engineered umbilical cord stem cell-derived exosomes direct tendon regeneration by mTOR signaling.Journal of nanobiotechnology · 2021Article
Corrections and comments
- Commented on by
Authors and funding
9 authors at 4 institutions in 4 countries.
Funding
Abstract
Fibrillin-1 (FBN1) deficiency-induced systemic sclerosis is attributed to elevation of interleukin-4 (IL4) and TGF-β, but the mechanism underlying FBN1 deficiency-associated osteopenia is not fully understood. We show that bone marrow mesenchymal stem cells (BMMSCs) from FBN1-deficient (Fbn1(+/-)) mice exhibit decreased osteogenic differentiation and increased adipogenic differentiation. Mechanistically, this lineage alteration is regulated by IL4/IL4Rα-mediated activation of mTOR signaling to down-regulate RUNX2 and up-regulate PPARγ2, respectively, via P70 ribosomal S6 protein kinase (P70S6K). Additionally, we reveal that activation of TGF-β/SMAD3/SP1 signaling results in enhancement of SP1 binding to the IL4Rα promoter to synergistically activate mTOR pathway in Fbn1(+/-) BMMSCs. Blockage of mTOR signaling by osteoblastic-specific knockout or rapamycin treatment rescues osteopenia phenotype in Fbn1(+/-) mice by improving osteogenic differentiation of BMMSCs. Collectively, this study identifies a previously unrecognized role of the FBN1/TGF-β/IL4Rα/mTOR cascade in BMMSC lineage selection and provides experimental evidence that rapamycin treatment may provide an anabolic therapy for osteopenia in Fbn1(+/-) mice.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.