Summary: An ADAMTS protease that contains two C-terminal thrombospondin (TS) motifs. It functions primarily as an aggrecanase, cleaving AGGRECAN in CARTILAGE, and may be involved in the destruction of aggrecan in ARTHRITIS.
Kintakas C, McCulloch D. Emerging roles for ADAMTS5 during development and disease. Matrix Biol. 2011;30:311-7 pubmed publisher
Yamamoto K, Santamaria S, Botkjaer K, Dudhia J, Troeberg L, Itoh Y, et al
. Inhibition of Shedding of Low-Density Lipoprotein Receptor-Related Protein 1 Reverses Cartilage Matrix Degradation in Osteoarthritis. Arthritis Rheumatol. 2017;69:1246-1256 pubmed publisher
..Shedding of LRP-1 is a key link to OA progression. Local inhibition of LRP-1 sheddase activities of ADAM-17 and MMP-14 is a unique way to reverse matrix degradation in OA cartilage and could be effective as a therapeutic approach. ..
Wilkinson D, Habgood A, Lamb H, Thompson P, Hawkins A, Desilets A, et al
. Matriptase Induction of Metalloproteinase-Dependent Aggrecanolysis In Vitro and In Vivo: Promotion of Osteoarthritic Cartilage Damage by Multiple Mechanisms. Arthritis Rheumatol. 2017;69:1601-1611 pubmed publisher
..Therapeutic targeting of matriptase proteolytic activity reduces metalloproteinase activity, further suggesting that this serine proteinase may have potential as a disease-modifying therapy in OA. ..
Ouhaddi Y, Nebbaki S, Habouri L, Afif H, Lussier B, Kapoor M, et al
. Exacerbation of Aging-Associated and Instability-Induced Murine Osteoarthritis With Deletion of D Prostanoid Receptor 1, a Prostaglandin D2 Receptor. Arthritis Rheumatol. 2017;69:1784-1795 pubmed publisher
..These findings indicate a critical role for DP1 signaling in OA pathogenesis. Modulation of the functions of DP1 may constitute a potential therapeutic target for the development of novel OA treatments. ..
Li F, Song R, Ao L, Reece T, Cleveland J, Dong N, et al
. ADAMTS5 Deficiency in Calcified Aortic Valves Is Associated With Elevated Pro-Osteogenic Activity in Valvular Interstitial Cells. Arterioscler Thromb Vasc Biol. 2017;37:1339-1351 pubmed publisher
..Matrilin 2 accumulation associated with relative ADAMTS5 deficiency may contribute to the mechanism underlying calcific aortic valve disease progression. ..
Durham T, Marimuthu J, Toth J, Liu C, Adams L, Mudra D, et al
. A Highly Selective Hydantoin Inhibitor of Aggrecanase-1 and Aggrecanase-2 with a Low Projected Human Dose. J Med Chem. 2017;60:5933-5939 pubmed publisher
..The projected human dose required to achieve sustained plasma levels ?10 times the hADAMTS-5 IC50 is 5 mg q.d. ..
Liu Y, Zhu H, Yan X, Gu H, Gu Z, Liu F. Endoplasmic reticulum stress participates in the progress of senescence and apoptosis of osteoarthritis chondrocytes. Biochem Biophys Res Commun. 2017;491:368-373 pubmed publisher
..These results help us to open new perspectives for the development of molecular-targeted treatment approaches and thus present an effective novel therapeutic approach for OA. ..