ArticleBiochimica et biophysica acta. Molecular cell research2017
AMPK downregulates ALK2 via increasing the interaction between Smurf1 and Smad6, leading to inhibition of osteogenic differentiation.
Article in Biochimica et biophysica acta. Molecular cell research, 2017. 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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Who cites it
19 citing papers in PubMed, 33 citations in OpenAlex.
- Aspirin prevents postoperative peritoneal adhesions by inhibiting the TGF‑β1/Smad signaling pathway in rats.Molecular medicine reports · 2026Article
- Regulatory Roles of E3 Ubiquitin Ligases and Deubiquitinases in Bone.Biomolecules · 2025Review
- New Insights into AMPK, as a Potential Therapeutic Target in Metabolic Dysfunction-Associated Steatotic Liver Disease and Hepatic Fibrosis.Biomolecules & therapeutics · 2025Review
- Review
- E3 ubiquitin ligases: key regulators of osteogenesis and potential therapeutic targets for bone disorders.Frontiers in cell and developmental biology · 2024Review
- Berberine and aspirin prevent traumatic heterotopic ossification by inhibition of BMP signalling pathway and osteogenic differentiation.Journal of cellular and molecular medicine · 2023Article
- The serum levels of activin A and bone morphogenetic protein-4 and -6 in patients with fibrodysplasia ossificans progressiva.Orphanet journal of rare diseases · 2023Article
- Pathophysiology and Emerging Molecular Therapeutic Targets in Heterotopic Ossification.International journal of molecular sciences · 2022Review
- Aspirin attenuates liver fibrosis by suppressing TGF‑β1/Smad signaling.Molecular medicine reports · 2022Article
- Metformin suppresses proliferation and differentiation induced by BMP9Frontiers in pharmacology · 2022Article
- Imbalance of TGF-β1/BMP-7 pathways induced by M2-polarized macrophages promotes hepatocellular carcinoma aggressiveness.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Berberine RepressesMolecular pharmacology · 2021Article
- Metformin attenuates trauma-induced heterotopic ossification via inhibition of Bone Morphogenetic Protein signalling.Journal of cellular and molecular medicine · 2020Article
- The deubiquitinating enzyme PSMD14 facilitates tumor growth and chemoresistance through stabilizing the ALK2 receptor in the initiation of BMP6 signaling pathway.EBioMedicine · 2019Article
- Targeting heterotopic ossification by inhibiting activin receptor‑like kinase 2 function (Review).Molecular medicine reports · 2019Review
- Review
- Perspectives of small molecule inhibitors of activin receptor‑like kinase in anti‑tumor treatment and stem cell differentiation (Review).Molecular medicine reports · 2019Review
- Role of Metformin on Osteoblast Differentiation in Type 2 Diabetes.BioMed research international · 2019Review
- Article
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Activin A receptor type I or activin receptor-like kinase 2 (ACVRI/ALK2) belongs to type I TGF-β family and plays an important role in bone development. Activating mutations of ALK2 containing the R206 to H mutation, are present in 95% in the rare autosomal genetic disease fibrodysplasia ossificans progressiva (FOP), which leads to the development of ectopic bone formation in muscle. The effect of AMP-activated protein kinase (AMPK) activation on ALK2R206H-mediated signaling in fibroblasts obtained from a FOP patient was assessed in the present study. The activity of the mutated ALK2 was suppressed by pharmacological AMPK activators such as metformin and aspirin, while their actions were blocked by the dominant negative mutant of AMPK and mimicked by the constitutively active mutant of AMPK. Furthermore, activation of AMPK upregulated Smad6 and Smurf1 and thereby enhanced their interactions, resulting in its proteosome-dependent degradation of ALK2. In contrast, knockdown of Smad6 or Smurf1 prevented metformin-induced reduction of ALK2. To evaluate the biological relevance of AMPK action on ALK2 activity, we induced FOP fibroblasts into iPS cells and found that their osteogenic differentiation in vitro was inhibited by metformin. Our studies provide novel insight into potential approaches to treatment of FOP, since several AMPK activators (e.g. metformin, berberine, and aspirin) are already in clinical use for the treatment of diabetes and metabolic syndromes.
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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.