ArticleAging2020
Indian Hedgehog regulates senescence in bone marrow-derived mesenchymal stem cell through modulation of ROS/mTOR/4EBP1, p70S6K1/2 pathway.
Article in Aging, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
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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.
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Who cites it
31 citing papers in PubMed, 42 citations in OpenAlex.
- Moderate neuroprotection of combination cell therapy in fetal growth restricted newborns at postnatal day 10.Stem cells translational medicine · 2026Article
- Anti-aging effect of Hedgehog signaling.Experimental & molecular medicine · 2026Review
- A Review of Ionizing Radiation-Induced Senescence of Bone Marrow Mesenchymal Stem/Stromal Cells: Mechanisms and Therapeutic Strategies.Current issues in molecular biology · 2026Review
- Bone Marrow Mesenchymal Stem Cell Senescence in the Development of Osteoporosis: Mechanisms, Interventions, and Future Directions.Current molecular medicine · 2026Review
- Addressing osteoblast senescence: Molecular pathways and the frontier of anti-ageing treatments.Clinical and translational medicine · 2025Review
- Pharmacokinetic characteristics of mesenchymal stem cells in translational challenges.Signal transduction and targeted therapy · 2024Review
- Hedgehog pathway and cancer: A new area (Review).Oncology reports · 2024Review
- A Mesenchymal stem cell Aging Framework, from Mechanisms to Strategies.Stem cell reviews and reports · 2024Review
- Skeletal phenotypes and molecular mechanisms in aging mice.Zoological research · 2024Review
- Engineering mesenchymal stem cells for premature ovarian failure: overcoming challenges and innovating therapeutic strategies.Theranostics · 2024Review
- mTOR signalling pathway in stem cell bioactivities and angiogenesis potential.Cell proliferation · 2023Review
- Distinct HAND2/HAND2-AS1 Expression Levels May Fine-Tune Mesenchymal and Epithelial Cell Plasticity of Human Mesenchymal Stem Cells.International journal of molecular sciences · 2023Article
- Cellular senescence in skeletal disease: mechanisms and treatment.Cellular & molecular biology letters · 2023Review
- Mesenchymal Stem Cell Senescence during Aging:From Mechanisms to Rejuvenation Strategies.Aging and disease · 2023Review
- mTOR Signaling Pathway in Bone Diseases Associated with Hyperglycemia.International journal of molecular sciences · 2023Review
- Mesenchymal Stromal Cells as a Driver of Inflammaging.International journal of molecular sciences · 2023Review
- Review
- Aging Hallmarks and the Role of Oxidative Stress.Antioxidants (Basel, Switzerland) · 2023Review
- Cellular microenvironment: a key for tuning mesenchymal stem cell senescence.Frontiers in cell and developmental biology · 2023Review
- Hedgehog Signalling Contributes to Trauma-Induced Tendon Heterotopic Ossification and Regulates Osteogenesis through Antioxidant Pathway in Tendon-Derived Stem Cells.Antioxidants (Basel, Switzerland) · 2022Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Premature senescence of bone marrow-derived mesenchymal stem cells (BMSC) remains a major concern for their application clinically. Hedgehog signaling has been reported to regulate aging-associated markers and MSC skewed differentiation. Indian Hedgehog (IHH) is a ligand of Hedgehog intracellular pathway considered as an inducer in chondrogenesis of human BMSC. However, the role of IHH in the aging of BMSC is still unclear. This study explored the role IHH in the senescence of BMSC obtained from human samples and senescent mice. Isolated BMSC were transfected with IHH siRNA or incubated with exogenous IHH protein and the mechanisms of aging and differentiation investigated. Moreover, the interactions between IHH, and mammalian target of rapamycin (mTOR) and reactive oxygen species (ROS) were evaluated using the corresponding inhibitors and antioxidants. BMSC transfected with IHH siRNA showed characteristics of senescence-associated features including increased senescence-associated β-galactosidase activity (SA-β-gal), induction of cell cycle inhibitors (p53/p16), development of senescence-associated secretory phenotype (SASP), activation of ROS and mTOR pathways as well as the promotion of skewed differentiation. Interestingly, BMSC treatment with IHH protein reversed the senescence markers and corrected biased differentiation. Moreover, IHH shortage-induced senescence signs were compromised after mTOR and ROS inhibition. Our findings presented anti-aging activity for IHH in BMSC through down-regulation of ROS/mTOR pathways. This discovery might contribute to increasing the therapeutic, immunomodulatory and regenerative potency of BMSC and introduce a novel remedy in the management of aging-related diseases.
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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.