ArticleChemistry & biology2014
Sulfated glycosaminoglycans control the extracellular trafficking and the activity of the metalloprotease inhibitor TIMP-3.
Article in Chemistry & biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 74 citations in OpenAlex.
- Heparan Sulfate Proteoglycans: Master Regulators of Cellular Signaling, Tissue Development, and Neural Function.Journal of neuroscience research · 2026Review
- Membrane-type I metalloproteinase (MT1-MMP): A key modifier of extracellular matrix microenvironment.The FEBS journal · 2026Review
- Glycosaminoglycan-functionalized hydrogels for sustained delivery of tissue inhibitor of metalloproteinase-3 mediating matrix metalloprotease inhibition and extracellular matrix stabilization.Bioactive materials · 2026Article
- The activity "blind spot": Why understanding which proteinases are active, not merely present, is essential for rigorous osteoarthritis research.Osteoarthritis and cartilage · 2026Review
- Advances in Extracellular Matrix Metalloproteinases: Implications for Renal Cell Carcinoma Pathophysiology, Diagnostics, and Therapeutics.Medicines (Basel, Switzerland) · 2026Review
- Exploratory transcriptomic analysis of mouse articular cartilage in response to tissue inhibitor of metalloproteinase 3 identifies inflammation-associated gene expression changes.Frontiers in immunology · 2026Article
- LRP1 Mediates Endocytosis Activity and Is a Potential Therapeutic Target in Osteoarthritis.Orthopaedic surgery · 2025Review
- Novel insights into the multifaceted and tissue-specific roles of the endocytic receptor LRP1.The Journal of biological chemistry · 2024Review
- Review: Mechanisms of TIMP-3 accumulation and pathogenesis in Sorsby fundus dystrophy.Molecular vision · 2024Review
- The Glycosaminoglycan Side Chains and Modular Core Proteins of Heparan Sulphate Proteoglycans and the Varied Ways They Provide Tissue Protection by Regulating Physiological Processes and Cellular Behaviour.International journal of molecular sciences · 2023Review
- Chemistry and Function of Glycosaminoglycans in the Nervous System.Advances in neurobiology · 2023Review
- Review
- Deglycosylation Increases the Aggregation and Angiogenic Properties of Mutant Tissue Inhibitor of Metalloproteinase 3 Protein: Implications for Sorsby Fundus Dystrophy.International journal of molecular sciences · 2022Article
- ADAM and ADAMTS disintegrin and metalloproteinases as major factors and molecular targets in vascular malfunction and disease.Advances in pharmacology (San Diego, Calif.) · 2022Article
- Targeting Dysregulation of Metalloproteinase Activity in Osteoarthritis.Calcified tissue international · 2021Review
- Serpins in cartilage and osteoarthritis: what do we know?Biochemical Society transactions · 2021Review
- Targeting Cartilage Degradation in Osteoarthritis.Pharmaceuticals (Basel, Switzerland) · 2021Review
- The Roles of Matrix Metalloproteinases and Their Inhibitors in Human Diseases.International journal of molecular sciences · 2020Review
- Failures of Endochondral Ossification in the Mucopolysaccharidoses.Current osteoporosis reports · 2020Review
- The retinal pigment epithelium in Sorsby Fundus Dystrophy shows increased sensitivity to oxidative stress-induced degeneration.Redox biology · 2020Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
Abstract
Tissue inhibitor of metalloproteinase 3 (TIMP-3) is an important regulator of extracellular matrix (ECM) turnover. TIMP-3 binds to sulfated ECM glycosaminoglycans or is endocytosed by cells via low-density lipoprotein receptor-related protein 1 (LRP-1). Here, we report that heparan sulfate (HS) and chondroitin sulfate E (CSE) selectively regulate postsecretory trafficking of TIMP-3 by inhibiting its binding to LRP-1. HS and CSE also increased TIMP-3 affinity for glycan-binding metalloproteinases, such as adamalysin-like metalloproteinase with thrombospondin motifs 5 (ADAMTS-5), by reducing the dissociation rate constants. The sulfation pattern was crucial for these activities because monosulfated or truncated heparin had a reduced ability to bind to TIMP-3 and increase its affinity for ADAMTS-5. Therefore, sulfation of ECM glycans regulates the levels and inhibitory activity of TIMP-3 and modulates ECM turnover, and small mimicries of sulfated glycans may protect the tissue from the excess destruction seen in diseases such as osteoarthritis, cancer, and atherosclerosis.
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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.