ArticleOncotarget2015
Modulation of TGFbeta 2 levels by lamin A in U2-OS osteoblast-like cells: understanding the osteolytic process triggered by altered lamins.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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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.
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Who cites it
19 citing papers in PubMed, 28 citations in OpenAlex.
- The Fall of the Armor: Lamin Dysregulation and a Wide Network of Laminopathies.Sub-cellular biochemistry · 2025Review
- The Role of Lamins in Genome Organisation: A Modelling Perspective.Sub-cellular biochemistry · 2025Review
- Lipodystrophic Laminopathies: From Dunnigan Disease to Progeroid Syndromes.International journal of molecular sciences · 2024Review
- Genetic reduction of mTOR extends lifespan in a mouse model of Hutchinson-Gilford Progeria syndrome.Aging cell · 2021Article
- Skeletal and Cardiac Muscle Disorders Caused by Mutations in Genes Encoding Intermediate Filament Proteins.International journal of molecular sciences · 2021Review
- Cutaneous and metabolic defects associated with nuclear abnormalities in a transgenic mouse model expressing R527H lamin A mutation causing mandibuloacral dysplasia type A (MADA) syndrome.Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology · 2020Article
- Lamin A/C and the Immune System: One Intermediate Filament, Many Faces.International journal of molecular sciences · 2020Review
- Altered adipocyte differentiation and unbalanced autophagy in type 2 Familial Partial Lipodystrophy: an in vitro and in vivo study of adipose tissue browning.Experimental & molecular medicine · 2019Article
- Cause and effect of microenvironmental acidosis on bone metastases.Cancer metastasis reviews · 2019Review
- Article
- The Cutting Edge: The Role of mTOR Signaling in Laminopathies.International journal of molecular sciences · 2019Review
- Lamins and bone disorders: current understanding and perspectives.Oncotarget · 2018Review
- Secretome analysis of in vitro aged human mesenchymal stem cells reveals IGFBP7 as a putative factor for promoting osteogenesis.Scientific reports · 2018Article
- Cardiolaminopathies from bench to bedside: challenges in clinical decision-making with focus on arrhythmia-related outcomes.Nucleus (Austin, Tex.) · 2018Review
- Elevated TGF β2 serum levels in Emery-Dreifuss Muscular Dystrophy: Implications for myocyte and tenocyte differentiation and fibrogenic processes.Nucleus (Austin, Tex.) · 2018Article
- Lipodystrophic syndromes due to LMNA mutations: recent developments on biomolecular aspects, pathophysiological hypotheses and therapeutic perspectives.Nucleus (Austin, Tex.) · 2018Review
- Extracellular matrix remodeling and transforming growth factor-β signaling abnormalities induced by lamin A/C variants that cause lipodystrophy.Journal of lipid research · 2017Article
- Causes and consequences of nuclear envelope alterations in tumour progression.European journal of cell biology · 2016Review
- Potential therapeutic effects of the MTOR inhibitors for preventing ageing and progeria-related disorders.British journal of clinical pharmacology · 2016Review
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transforming growth factor beta (TGFbeta) plays an essential role in bone homeostasis and deregulation of TGFbeta occurs in bone pathologies. Patients affected by Mandibuloacral Dysplasia (MADA), a progeroid disease linked to LMNA mutations, suffer from an osteolytic process. Our previous work showed that MADA osteoblasts secrete excess amount of TGFbeta 2, which in turn elicits differentiation of human blood precursors into osteoclasts. Here, we sought to determine how altered lamin A affects TGFbeta signaling. Our results show that wild-type lamin A negatively modulates TGFbeta 2 levels in osteoblast-like U2-OS cells, while the R527H mutated prelamin A as well as farnesylated prelamin A do not, ultimately leading to increased secretion of TGFbeta 2. TGFbeta 2 in turn, triggers the Akt/mTOR pathway and upregulates osteoprotegerin and cathepsin K. TGFbeta 2 neutralization rescues Akt/mTOR activation and the downstream transcriptional effects, an effect also obtained by statins or RAD001 treatment. Our results unravel an unexpected role of lamin A in TGFbeta 2 regulation and indicate rapamycin analogs and neutralizing antibodies to TGFbeta 2 as new potential therapeutic tools for MADA.
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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.