ArticleArthritis and rheumatism2008
Induction of an osteoarthritis-like phenotype and degradation of phosphorylated Smad3 by Smurf2 in transgenic mice.
Article in Arthritis and rheumatism, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 1 of them a synthesis that pooled it.
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.
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Who cites it
68 citing papers in PubMed, 1 synthesis or guideline pooled it, 120 citations in OpenAlex.
- Association between SMAD3 gene polymorphisms and osteoarthritis risk: a systematic review and meta-analysis.Journal of orthopaedic surgery and research · 2018Pooled it
- TGF-β/BMP signaling in skeletal biology: molecular mechanisms, regulatory networks, and therapeutic implications in development, regeneration, and disease.Bone research · 2026Review
- Evaluating Knee Osteoarthritis Induction Methods in Small Translational Animal Models from 1970-2025: A Comprehensive Systematic Review.The archives of bone and joint surgery · 2026Review
- Signalling interaction between β-catenin and other signalling molecules during osteoarthritis development.Cell proliferation · 2024Review
- The roles and regulatory mechanisms of TGF-β and BMP signaling in bone and cartilage development, homeostasis and disease.Cell research · 2024Review
- The role of E3 ubiquitin ligases in bone homeostasis and related diseases.Acta pharmaceutica Sinica. B · 2023Review
- The role of TGF-beta3 in cartilage development and osteoarthritis.Bone research · 2023Review
- Elucidating the role of ubiquitination and deubiquitination in osteoarthritis progression.Frontiers in immunology · 2023Review
- Tissue mechanics coevolves with fibrillar matrisomes in healthy and fibrotic tissues.Matrix biology : journal of the International Society for Matrix Biology · 2022Review
- PTHrP promotes subchondral bone formation in TMJ-OA.International journal of oral science · 2022Article
- miR-29b inhibits TGF-β1-induced cell proliferation in articular chondrocytes.Biochemistry and biophysics reports · 2022Article
- Inhibition of transforming growth factor-β in osteoarthritis. Discrepancy with reduced TGFβ signaling in normal joints.Osteoarthritis and cartilage open · 2022Review
- β2-microglobulin alters the profiles of inflammatory cytokines and of matrix metalloprotease in macrophages derived from the osteoarthritic synovium.Central-European journal of immunology · 2022Article
- SMURF1 and SMURF2 in Progenitor Cells from Articular Cartilage and Meniscus during Late-Stage Osteoarthritis.Cartilage · 2021Article
- Circ_0116061 regulated the proliferation, apoptosis, and inflammation of osteoarthritis chondrocytes through regulating the miR-200b-3p/SMURF2 axis.Journal of orthopaedic surgery and research · 2021Article
- Mechanical stress determines the configuration of TGFβ activation in articular cartilage.Nature communications · 2021Article
- Mechanosensitive Control of Articular Cartilage and Subchondral Bone Homeostasis in Mice Requires Osteocytic Transforming Growth Factor β Signaling.Arthritis & rheumatology (Hoboken, N.J.) · 2021Article
- Promising targets for therapy of osteoarthritis: a review on the Wnt and TGF-β signalling pathways.Therapeutic advances in musculoskeletal disease · 2021Review
- Standardized Histomorphometric Evaluation of Osteoarthritis in a Surgical Mouse Model.Journal of visualized experiments : JoVE · 2020Article
- HECT E3 ubiquitin ligases - emerging insights into their biological roles and disease relevance.Journal of cell science · 2020Review
8 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
objectiveTo determine whether Smurf2, an E3 ubiquitin ligase known to inhibit transforming growth factor beta (TGFbeta) signaling, is expressed in human osteoarthritic (OA) cartilage and can initiate OA in mice.
methodsHuman OA cartilage was obtained from patients undergoing knee arthroplasty. Samples were graded histologically using the Mankin scale and were examined immunohistochemically for Smurf2 expression. A transgene driven by the collagen 2alpha1 promoter was used to overexpress Smurf2 in mice. Smurf2 overexpression in mouse sternal chondrocytes was confirmed by reverse transcription-polymerase chain reaction and Western blotting. Changes in articular cartilage area, chondrocyte number, and chondrocyte diameter were assessed histomorphometrically using OsteoMeasure software. Alterations in type X collagen and matrix metalloproteinase 13 (MMP-13) in articular chondrocytes were examined by in situ hybridization and immunohistochemistry, respectively. Joint bone phenotypes were evaluated by microfocal computed tomography. The effects of Smurf2 overexpression on TGFbeta signaling were examined using a luciferase-based reporter and immunoprecipitation/Western blotting.
resultsHuman OA cartilage strongly expressed Smurf2 as compared with nonarthritic human cartilage. By 8 months of age, Smurf2-transgenic mice exhibited decreased articular cartilage area, fibrillation, clefting, eburnation, subchondral sclerosis, and osteophytes. Increased expression of type X collagen and MMP-13 were also detected in articular cartilage from transgenic mice. Transgenic sternal chondrocytes showed reduced TGFbeta signaling as well as decreased expression and increased ubiquitination of pSmad3.
conclusionSmurf2 is up-regulated during OA in humans, and Smurf2-transgenic mice spontaneously develop an OA-like phenotype that correlates with decreased TGFbeta signaling and increased pSmad3 degradation. Overall, these results suggest a role of Smurf2 in the pathogenesis of OA.
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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.