ArticleScientific reports2020
Aggrecanase-selective tissue inhibitor of metalloproteinase-3 (TIMP3) protects articular cartilage in a surgical mouse model of osteoarthritis.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
- Critical Overview of Molecular Insights into Osteoarthritis and Therapeutic Targets: Cytokines, RANKL, MMPs, Adipokines and Phosphate Dysregulation.International journal of molecular sciences · 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
- Ectopic Adrenocortical Adenoma Causing Malignant Hypertension and Hypokalemia.The American journal of case reports · 2025Article
- Filtered and unfiltered lipoaspirates reveal novel molecular insights and therapeutic potential for osteoarthritis treatment: a preclinicalFrontiers in cell and developmental biology · 2025Article
- The TIMP protein family: diverse roles in pathophysiology.American journal of physiology. Cell physiology · 2024Review
- Evaluation of mechanistic serum and urine biomarkers for secondary osteoarthritis associated with developmental dysplasia of the hip.Journal of orthopaedics · 2023Article
- Targeting Aggrecanases for Osteoarthritis Therapy: From Zinc Chelation to Exosite Inhibition.Journal of medicinal chemistry · 2022Review
- Krüppel-like factor-4 and Krüppel-like factor-2 are important regulators of joint tissue cells and protect against tissue destruction and inflammation in osteoarthritis.Annals of the rheumatic diseases · 2022Article
- ADAMTS-4 as a possible distinguishing indicator between osteoarthritis and haemophilic arthropathy.Haemophilia : the official journal of the World Federation of Hemophilia · 2022Article
- Targeting matrix metalloproteases: A promising strategy for herbal medicines to treat rheumatoid arthritis.Frontiers in immunology · 2022Review
- Article
- Targeting Dysregulation of Metalloproteinase Activity in Osteoarthritis.Calcified tissue international · 2021Review
- Metalloelastase-12 is involved in the temporomandibular joint inflammatory response as well as cartilage degradation by aggrecanases in STR/Ort mice.Biomedical reports · 2021Article
- Osteoarthritis: Novel Molecular Mechanisms Increase Our Understanding of the Disease Pathology.Journal of clinical medicine · 2021Review
- Strategies to Target ADAM17 in Disease: From its Discovery to the iRhom Revolution.Molecules (Basel, Switzerland) · 2021Review
- Regulation of ADAMTS Proteases.Frontiers in molecular biosciences · 2021Review
- Effects of Diet Induced Weight Reduction on Cartilage Pathology and Inflammatory Mediators in the Joint Tissues.Frontiers in medicine · 2021Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
A key feature of osteoarthritis is the gradual loss of articular cartilage and bone deformation, resulting in the impairment of joint function. The primary cause of cartilage destruction is considered to be the presence of elevated proteases, such as matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs). However, clinically tested global MMP inhibitors have low efficacy that may be due to their lack of selectivity. We previously demonstrated in vitro that a variant of tissue inhibitor of metalloproteinase-3 ([-1A]TIMP3) inhibits ADAMTSs but not MMPs. In this study, we tested whether the selectivity of [-1A]TIMP3 is beneficial compared with that of the wild-type TIMP3 in preventing or delaying the onset of the degenerative effects in a mouse model of osteoarthritis. We generated transgenic mice that overexpressed TIMP3 or [-1A]TIMP3 driven by a chondrocyte-specific type II collagen promoter. TIMP3 transgenic mice showed compromised bone integrity as opposed to [-1A]TIMP3 mice. After surgically induced joint instability, TIMP3 overexpression proved to be less protective in cartilage destruction than [-1A]TIMP3 at late stages of OA. The selective inhibition of ADAMTSs provides the possibility of modifying TIMP3 to specifically target a class of cartilage-degrading proteinases and to minimize adverse effects on bone and possibly other tissues.
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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.