ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2013
LRP-1-mediated endocytosis regulates extracellular activity of ADAMTS-5 in articular cartilage.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 107 citations in OpenAlex.
- The von Willebrand factor A-1 domain binding aptamer BT200 elevates plasma levels of von Willebrand factor and factor VIII: a first-in-human trial.Haematologica · 2022Trial
- The activity "blind spot": Why understanding which proteinases are active, not merely present, is essential for rigorous osteoarthritis research.Osteoarthritis and cartilage · 2026Review
- Conditional knockout of membrane-type I matrix metalloproteinase in smooth muscle cells of adult mice alleviates atherosclerosis without affecting basic cardiovascular function.Clinical and translational medicine · 2026Article
- The ADAMTS family: from extracellular matrix proteases to orchestrators of fibrosis.Cell communication and signaling : CCS · 2026Review
- Design, synthesis and biological activity of glycoconjugated ADAMTS5 exosite inhibitors: applications in osteoarthritis and ovarian cancer models.Scientific reports · 2025Article
- Mesenchymal stem cells and extracellular vesicles for knee osteoarthritis: clinical application, mechanism exploration and prospect.Stem cell research & therapy · 2025Review
- Article
- The protease ADAMTS5 controls ovarian cancer cell invasion, downstream of Rab25.The FEBS journal · 2025Article
- LRP1 Mediates Endocytosis Activity and Is a Potential Therapeutic Target in Osteoarthritis.Orthopaedic surgery · 2025Review
- Skeletal progenitor LRP1 deficiency causes severe and persistent skeletal defects with Wnt pathway dysregulation.Bone research · 2025Article
- LRP1 mitigates intervertebral disc degeneration by inhibiting endoplasmic reticulum stress through stabilizing the PPARγ.Journal of orthopaedic translation · 2025Article
- Translational pharmacokinetic and pharmacodynamic modelling of the anti-ADAMTS-5 NANOBODYJournal of pharmacokinetics and pharmacodynamics · 2024Article
- Engineering exosomes derived from TNF-α preconditioned IPFP-MSCs enhance both yield and therapeutic efficacy for osteoarthritis.Journal of nanobiotechnology · 2024Article
- Novel insights into the multifaceted and tissue-specific roles of the endocytic receptor LRP1.The Journal of biological chemistry · 2024Review
- Potential Targeting Mechanisms for Bone-Directed Therapies.International journal of molecular sciences · 2024Review
- ADAMTS4 is a crucial proteolytic enzyme for versican cleavage in the amnion at parturition.Communications biology · 2024Article
- ADAMTS-1 has nuclear localization in cells with epithelial origin and leads to decreased cell migration.Experimental cell research · 2023Article
- Healthy and Osteoarthritis-Affected Joints Facing the Cellular Crosstalk.International journal of molecular sciences · 2023Review
- Review
- Biomimetic Scaffolds Modulate the Posttraumatic Inflammatory Response in Articular Cartilage Contributing to Enhanced Neoformation of Cartilaginous Tissue In Vivo.Advanced healthcare materials · 2022Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Aggrecan is a major matrix component of articular cartilage, and its degradation is a crucial event in the development of osteoarthritis (OA). Adamalysin-like metalloproteinase with thrombospondin motifs 5 (ADAMTS-5) is a major aggrecan-degrading enzyme in cartilage, but there is no clear correlation between ADAMTS-5 mRNA levels and OA progression. Here, we report that post-translational endocytosis of ADAMTS-5 by chondrocytes regulates its extracellular activity. We found 2- to 3-fold reduced aggrecanase activity when ADAMTS-5 was incubated with live porcine cartilage, resulting from its rapid endocytic clearance. Studies using receptor-associated protein (RAP), a ligand-binding antagonist for the low-density lipoprotein receptor-related proteins (LRPs), and siRNA-mediated gene silencing revealed that the receptor responsible for ADAMTS-5 clearance is LRP-1. Domain-deletion mutagenesis of ADAMTS-5 identified that the noncatalytic first thrombospondin and spacer domains mediate its endocytosis. The addition of RAP to porcine cartilage explants in culture increased the basal level of aggrecan degradation, as well as ADAMTS-5-induced aggrecan degradation. Notably, LRP-1-mediated endocytosis of ADAMTS-5 is impaired in chondrocytes of OA cartilage, with ∼90% reduction in protein levels of LRP-1 without changes in its mRNA levels. Thus, LRP-1 dictates physiological and pathological catabolism of aggrecan in cartilage as a key modulator of the extracellular activity of ADAMTS-5.
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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.