ArticleThe Journal of biological chemistry2008
Ubiquitin ligase Smurf1 mediates tumor necrosis factor-induced systemic bone loss by promoting proteasomal degradation of bone morphogenetic signaling proteins.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 139 citations in OpenAlex.
- Beyond resorption-driven coupling: a multi-layered framework for osteoclast-osteoblast communication and its therapeutic consequences.Frontiers in endocrinology · 2026Review
- Smurf1 promotes gastric cancer progression by regulating Axin2-dependent Wnt signaling pathway.Scientific reports · 2025Article
- Priming of mouse pre-osteoblasts with Interleukin-3 attenuates TNF-α-induced-inhibition of osteoblast differentiation.BMC musculoskeletal disorders · 2025Article
- Addressing the challenges of infectious bone defects: a review of recent advances in bifunctional biomaterials.Journal of nanobiotechnology · 2025Review
- Smurf1-targeting microRNA-136-5p-modified bone marrow mesenchymal stem cells combined with 3D-printed β-tricalcium phosphate scaffolds strengthen osteogenic activity and alleviate bone defects.The Kaohsiung journal of medical sciences · 2024Article
- Anti-NF-κB peptide derived from nuclear acidic protein attenuates ovariectomy-induced osteoporosis in mice.JCI insight · 2023Article
- Dual-functional composite scaffolds for inhibiting infection and promoting bone regeneration.Materials today. Bio · 2022Review
- Inhibition of Neddylation Suppresses Osteoclast Differentiation and Function In Vitro and Alleviates Osteoporosis In Vivo.Biomedicines · 2022Article
- NEDD4 E3 Ligases: Functions and Mechanisms in Bone and Tooth.International journal of molecular sciences · 2022Review
- Role of the Interaction of Tumor Necrosis Factor-α and Tumor Necrosis Factor Receptors 1 and 2 in Bone-Related Cells.International journal of molecular sciences · 2022Review
- Genome-Wide CRISPR/Cas9-Based Screening for Deubiquitinase Subfamily Identifies Ubiquitin-Specific Protease 11 as a Novel Regulator of Osteogenic Differentiation.International journal of molecular sciences · 2022Article
- E3 Ubiquitin Ligases: Potential Therapeutic Targets for Skeletal Pathology and Degeneration.Stem cells international · 2022Review
- Proteasome inhibition-enhanced fracture repair is associated with increased mesenchymal progenitor cells in mice.PloS one · 2022Article
- SMURF1, a promoter of tumor cell progression?Cancer gene therapy · 2021Review
- Exploring the Roles of HERC2 and the NEDD4L HECT E3 Ubiquitin Ligase Subfamily in p53 Signaling and the DNA Damage Response.Frontiers in oncology · 2021Review
- Delivery of RNAi-Based Therapeutics for Bone Regeneration.Current osteoporosis reports · 2020Review
- Non-viral Gene Delivery of Interleukin-1 Receptor Antagonist Using Collagen-Hydroxyapatite Scaffold Protects Rat BM-MSCs From IL-1β-Mediated Inhibition of Osteogenesis.Frontiers in bioengineering and biotechnology · 2020Article
- Review
- Targeting tumor necrosis factor receptors in ankylosing spondylitis.Annals of the New York Academy of Sciences · 2019Review
- MicroRNA-672-5p Identified during Weaning Reverses Osteopenia and Sarcopenia in Ovariectomized Mice.Molecular therapy. Nucleic acids · 2019Article
15 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
Chronic inflammatory disorders, such as rheumatoid arthritis, are often accompanied by systemic bone loss, which is thought to occur through inflammatory cytokine-mediated stimulation of osteoclast resorption and inhibition of osteoblast function. However, the mechanisms involved in osteoblast inhibition remain poorly understood. Here we test the hypothesis that increased Smad ubiquitin regulatory factor 1 (Smurf1)-mediated degradation of the bone morphogenetic protein pathway signaling proteins mediates reduced bone formation in inflammatory disorders. Osteoblasts derived from bone marrow or long bone samples of adult tumor necrosis factor (TNF) transgenic (TNF-Tg) mice were used in this study. TNF decreased the steady-state levels of Smad1 and Runx2 protein similarly to those in long bones of TNF-Tg mice. In the presence of the proteasome inhibitor MG132, TNF increased accumulation of ubiquitinated Smad1 protein. TNF administration over calvarial bones caused decreases in Smad1 and Runx2 protein levels and mRNA expression of osteoblast marker genes in wild-type, but not in Smurf1(-/-) mice. Vertebral bone volume and strength of TNF-Tg/Smurf1(-/-) mice were examined by a combination of micro-CT, bone histomorphometry, and biomechanical testing and compared with those from TNF-Tg littermates. TNF-Tg mice had significantly decreased bone volume and biomechanical properties, which were partially rescued in TNF-Tg/Smurf1(-/-) mice. We conclude that in chronic inflammatory disorders where TNF is increased, TNF induces the expression of ubiquitin ligase Smurf1 and promotes ubiquitination and proteasomal degradation of Smad1 and Runx2, leading to systemic bone loss. Inhibition of ubiquitin-mediated Smad1 and Runx2 degradation in osteoblasts could help to treat inflammation-induced osteoporosis.
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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.