Deletion of active ADAMTS5 prevents cartilage degradation in a murine model of osteoarthritis

By Kohki Kawane, M. Ohtani, Keiko Miwa, Takuji Kizawa, Yoshiyuki Kanbara, Yoshichika Yoshioka, Hideki Yoshikawa, Shigekazu Nagata. Nature, 2005

1,298 citations recorded by the source corpus.

Subfields: Cancer Research, Immunology and Allergy, Rheumatology

View Paper: https://www.semanticscholar.org/paper/1e56aa1d5b43abde811bbe1d7be3da15d4c8352e

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

1. C. Malemud
2. Shizuo Akira
3. S. Apte
4. D. Edwards
5. TA Wynn
6. K. Takeda
7. Taro Kawai
8. R. Medzhitov

In Immunology and Allergy

1. T. Mead
2. S. Apte

In Rheumatology

1. S. Goldring
2. M. Goldring
3. P. Murray
4. Richard F. Loeser
5. TA Wynn
6. Shizuo Akira

Citations in the corpus

• Osteoarthritis: a disease of the joint as an organ. (2012, background): “The importance of proteoglycan depletion in cartilage erosion was demonstrated in Adamts5 knockout mice, which are protected against progression in the surgical OA model (8).”
• Matrix metalloproteinases (MMPs) in health and disease: an overview. (2006, background): “Of note, no specific murine growth plate defects were described resulting from deletion of the ADAMTS-4 or ADAMTS-5 genes (24, 25) despite strong evidence that ADAMTS -4 and -5 play a critical role in articular cartilage degeneration in osteoarthritis (OA).”
• Calcium pentosan polysulfate directly inhibits enzymatic activity of ADAMTS4 (aggrecanase‐1) in osteoarthritic chondrocytes (2008, background): “studies using ADAMTS4 (also called aggrecanase-1) and ADAMTS5 (aggrecanase-2) knockout mice have indicated that ADAMTS5 is responsible for cartilage destruction by aggrecan degradation in mice [ 3 ,4].”
• Oxidative Stress and Inflammation in Osteoarthritis Pathogenesis: Role of Polyphenols (2020, background): “A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript inflammatory cytokine and chemokine genes, iNOS and COX-2 and increased expression of cartilage ECM degrading proteases such as MMP-1, MMP-9, MMP-13, ADAMTS4, and ADAMTS5 [77].”
• ADAMTS proteins in human disorders (2018, background): “Since ADAMTS5 is indisputably causal in cartilage aggrecan destruction in osteoarthritis (OA) [44, 45], association of the conjoint locus for ADAMTS5 and another aggrecanase, ADAMTS1 in degenerative disk disease [46, 47] is intriguing, since the intervertebral disk is similar in its composition to c”
• Osteoarthritis: pathogenic signaling pathways and therapeutic targets (2023, background): “ADAMTS5 deletion protected joints from cartilage destruction in surgically induced mouse OA model.(422,423) The phase II clinical trials of the film-coated tablets GLPG1972/ S201086, which is developed as an ADAMTS5 inhibitor for oral use for OA treatment finished in July 2021 (NCT03595618).”
• Mitochondrial DNA That Escapes from Autophagy Causes Inflammation and Heart Failure (2012, methodology): “To identify the source of IL-1b and IL-6, we performed in situ hybridization analysis in heart sections.”
• Cartilage homeostasis in health and rheumatic diseases (2009, neutral): “Plaas A, Osborn B, Yoshihara Y, Bai Y, Bloom T, Nelson F, Mikecz K, Sandy JD: Aggrecanolysis in human osteoarthritis: confocal localization and biochemical characterization of ADAMTS5hyaluronan complexes in articular cartilages.”
• Protective and pathogenic functions of macrophage subsets (2011, background): “M1-like macrophage-derived TNF, IL-18, IL-12 and IL-23 have been identified as important mediators in several chronic inflammatory and autoimmune diseases, including Crohn's disease, rheumatoid arthritis, multiple sclerosis and autoimmune hepatiti”