ArticleThe Journal of clinical investigation2007
Blocking aggrecanase cleavage in the aggrecan interglobular domain abrogates cartilage erosion and promotes cartilage repair.
Article in The Journal of clinical investigation, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 79 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
79 citing papers in PubMed, 195 citations in OpenAlex.
- Proteolysis at the extracellular matrix interface: Molecular architects and regulators in health and disease.The FEBS journal · 2026Review
- An Overview of ADAMTS Proteases.Methods in molecular biology (Clifton, N.J.) · 2026Review
- Evaluation of the anti-RANKL monoclonal antibody in rheumatoid arthritis rats.Archives of rheumatology · 2023Article
- The adaptive response of the mandibular condyle to increased load is disrupted by ADAMTS5 deficiency.Connective tissue research · 2023Article
- The Mechanism and Role of ADAMTS Protein Family in Osteoarthritis.Biomolecules · 2022Review
- Methods for isolating and analyzing physiological hyaluronan: a review.American journal of physiology. Cell physiology · 2022Review
- Elevation of MMP1 and ADAMTS5 mRNA expression in glenohumeral synovia of patients with hypercholesterolemia.Journal of orthopaedic surgery and research · 2022Article
- Blood and urine biomarkers in osteoarthritis - an update on cartilage associated type II collagen and aggrecan markers.Current opinion in rheumatology · 2022Review
- Hyaluronic Acid-Binding, Anionic, Nanoparticles Inhibit ECM Degradation and Restore Compressive Stiffness in Aggrecan-Depleted Articular Cartilage Explants.Pharmaceutics · 2021Article
- Targeting Dysregulation of Metalloproteinase Activity in Osteoarthritis.Calcified tissue international · 2021Review
- Development of a highly sensitive chemiluminescence immunoassay for quantification of aggrecanase-generated ARGS aggrecan fragments in serum.Osteoarthritis and cartilage open · 2021Article
- A new mouse mutant with cleavage-resistant versican and isoform-specific versican mutants demonstrate that proteolysis at the GluMatrix biology plus · 2021Article
- Hyalectanase Activities by the ADAMTS Metalloproteases.International journal of molecular sciences · 2021Review
- From Pathogenesis to Therapy in Knee Osteoarthritis: Bench-to-Bedside.International journal of molecular sciences · 2021Review
- ADAMTS proteases and the tumor immune microenvironment: Lessons from substrates and pathologies.Matrix biology plus · 2021Review
- Proinflammatory T cell polarization is already present in patients with early knee osteoarthritis.Arthritis research & therapy · 2021Article
- Exosite inhibition of ADAMTS-5 by a glycoconjugated arylsulfonamide.Scientific reports · 2021Article
- ADAMTS5 in Osteoarthritis: Biological Functions, Regulatory Network, and Potential Targeting Therapies.Frontiers in molecular biosciences · 2021Review
- The quest for substrates and binding partners: A critical barrier for understanding the role of ADAMTS proteases in musculoskeletal development and disease.Developmental dynamics : an official publication of the American Association of Anatomists · 2021Review
- Pathogenesis of Osteoarthritis: Risk Factors, Regulatory Pathways in Chondrocytes, and Experimental Models.Biology · 2020Review
19 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aggrecan loss from cartilage in arthritis is mediated by aggrecanases. Aggrecanases cleave aggrecan preferentially in the chondroitin sulfate-2 (CS-2) domain and secondarily at the E(373) downward arrow(374)A bond in the interglobular domain (IGD). However, IGD cleavage may be more deleterious for cartilage biomechanics because it releases the entire CS-containing portion of aggrecan. Recent studies identifying aggrecanase-2 (ADAMTS-5) as the predominant aggrecanase in mouse cartilage have not distinguished aggrecanolysis in the IGD from aggrecanolysis in the CS-2 domain. We generated aggrecan knockin mice with a mutation that rendered only the IGD resistant to aggrecanases in order to assess the contribution of this specific cleavage to cartilage pathology. The knockin mice were viable and fertile. Aggrecanase cleavage in the aggrecan IGD was not detected in knockin mouse cartilage in situ nor following digestion with ADAMTS-5 or treatment of cartilage explant cultures with IL-1 alpha. Blocking cleavage in the IGD not only diminished aggrecan loss and cartilage erosion in surgically induced osteoarthritis and a model of inflammatory arthritis, but appeared to stimulate cartilage repair following acute inflammation. We conclude that blocking aggrecanolysis in the aggrecan IGD alone protects against cartilage erosion and may potentiate cartilage repair.
Indexed as
Identifiers
What OpenQuestion holds
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.