ADAMTS5 is the major aggrecanase in mouse cartilage in vivo and in vitro

By H. Stanton, F. Rogerson, C. East, S. Golub, K. Lawlor, Clare T. Meeker, C. Little, K. Last, P. Farmer, I. Campbell and 2 more. Nature, 2005

923 citations recorded by the source corpus.

Subfields: Cancer Research, Immunology and Allergy, Rheumatology

View Paper: https://www.semanticscholar.org/paper/0f3b825500b8aa9e6a2b565447438bd8e7565b2d

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In Cancer Research

1. S. Apte
2. D. Edwards
3. Gary S. Firestein

In Immunology and Allergy

1. T. Mead
2. S. Apte

In Rheumatology

1. B. Bartok
2. M. Goldring
3. Gary S. Firestein
4. K. Marcu

Citations in the corpus

• The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) family (2015, background): “In mice, however, ADAMTS5 alone is the critical enzyme, as Adamts5−/− mice show significantly reduced joint destruction when compared to wild-type or Adamts4−/− mice in surgical and allergeninduced models of arthritis (Table 2) [102, 103].”
• Fibroblast-like synoviocytes: key effector cells in rheumatoid arthritis (2010, background): “This growth factor is present in rheumatoid synovial effusions and synoviocytes in the intimal lining could contribute to the loss of proteoglycan in cartilage (67, 68).”
• Matrix metalloproteinases. (2010, background): “A large number of papers reference the biological and biochemical properties of MMPs because of their association with physiological and pathological diseases such as cancer [9-18].”
• 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).”
• 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”
• Cartilage homeostasis in health and rheumatic diseases (2009, positive): “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.”
• 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 ].”
• Biosynthesis and Expression of a Disintegrin-like and Metalloproteinase Domain with Thrombospondin-1 Repeats-15 (2013, background): “In contrast, the inactivation ofAdamts5 confers protection against experimentally induced arthritis in the mouse through an apparent lack of aggrecan cleavage in synovial joints (20, 21), making ADAMTS5 a major drug target for arthritis intervention.”
• Partially redundant functions of Adamts1 and Adamts4 in the perinatal development of the renal medulla (2011, background): “However, more recent studies involving the generation of Adamts4 and Adamts5 knockout mice showed that Adamts5 is of much greater importance in the metabolism of cartilage ACAN, whereas Adamts4 appears expendable (Glasson et al., 2004; Majumdar et al., 2007; Stanton et al., 2005).”