China 
Africa 
Explore chapters and articles related to this topic
Osteoarthritis
Published in Kohlstadt Ingrid, Cintron Kenneth, Metabolic Therapies in Orthopedics, Second Edition, 2018
David Musnick, Richard D. Batson
Crystalline stabilized GS has been shown to inhibit IL-1β-induced gene expression of matrix degradation factors MMP-3 (stromelysin-1) and ADAMTS-5 (aggrecanase 2), thus having an effect of decreasing enzyme mediated chondrocyte degradation (Chiusaroli et al., 2011). Crystalline stabilized GS was introduced in studies as the “Dona” form. Other companies now have stabilized GS. When prescribing GS it is important to ask a company if their GS is stabilized.
Basic Science of Osteoarthritis
Published in Manoj Ramachandran, Tom Nunn, Basic Orthopaedic Sciences, 2018
Inflammatory cytokines are critical mediators in the disturbed metabolism and enhanced catabolism of OA. Interleukin (IL)-1β seems to be the main pro-catabolic cytokine involved in the pathophysiology of OA, complemented by tumour necrosis factor (TNF)-alpha and IL-6. They enhance the production and activity of MMPs and aggrecanase, and reduce chondrocyte synthesis of proteoglycan and type II collagen. IL-4 and IL-10 are thought to have a chondroprotective function.
Articular Cartilage Pathology and Therapies
Published in Kyriacos A. Athanasiou, Eric M. Darling, Grayson D. DuRaine, Jerry C. Hu, A. Hari Reddi, Articular Cartilage, 2017
Kyriacos A. Athanasiou, Eric M. Darling, Grayson D. DuRaine, Jerry C. Hu, A. Hari Reddi
How, then, does inflammation wreak such havoc on this tissue? As the disease progresses, the thickening and increasingly hypervascular synovium secretes MMPs and aggrecanases. The cleavage of aggrecan and the subsequent degradation of compressive properties are mediated by these aggrecanases. Aggrecanases belong to the A Disintegrin and Metalloproteinase with Thrombospondin motifs (ADAMTS) family, which includes ADAMTS4 and 5 (aggrecanase 1 and 2, respectively). IL-1 and TNF-α modulate the expression of ADAMTS4 to induce catabolism (Tortorella et al. 2001). However, ADAMTS5 is constitutively expressed (McCulloch et al. 2009); it must be remembered, though, given the shorter half-life of aggrecan, that both aggrecanases have natural functions in tissue remodeling in healthy tissue, versus their function in the disease state.
The collagenases: are they tractable targets for preventing cartilage destruction in osteoarthritis?
Published in Expert Opinion on Therapeutic Targets, 2022
Tuomo Karila, Taina Tervahartiala, Beniamin Cohen, Timo Sorsa
OA is a complex multifactorial disease with a profound genetic component [3,4]. OA is more delimiting person’s activity than heart disease, hypertension, blindness, or diabetes [5]. The definitive pathomechanism of this highly prevalent disease and its irreversible progression have not been fully elucidated [6–8]. At this stage, we do not have a disease modifying drug for the treatment of OA. Inhibitors of collagenases, more precisely matrix metalloproteinase (MMP) −1, −8, −13, seem to be a very promising candidates for treating the disease due to the fact that they are regarded to exert the potential to halt a progression of AC degradation in various stages. A cartilage protective medication that down-regulates collagenase production or activity should be effective, and especially as MMP-13 is regarded as a major type II collagen-degrading collagenase [9]. Also an aggrecanase, which targets mostly cartilage proteoglycans with a role in the OA development, is de-novo and in-situ expressed by osteoarthritis-affected articular resident cells in the joint [9]. Therefore, we have put more emphasis on controlling of MMP-13ʹs activity as an attractive target for OA treatment. Nevertheless, also collagenolytic cathepsin K, as a non-MMP protease, has been included in the discussion.
Are serum levels of ADAMTS5, TAS and TOS at 24–28 gestational weeks associated with adverse perinatal outcomes in gestational diabetic women?
Published in Journal of Obstetrics and Gynaecology, 2020
Sibel Ozler, Efser Oztas, Basak Gumus Guler, Ozcan Erel, Ali Turhan Caglar, Merve Ergin, Dilek Uygur, Nuri Danisman
ECM remodeling is controlled by specific proteases and various members of A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) enzymes are known to function in the cleavage and degradation of ECM components (Gabbay-Benziv and Baschat 2015). Some ADAMTS subtypes such as ADAMTS5 and ADAMTS11 were shown to play important roles in implantation and placentation processes by the studies of term human placenta and uterine tissues (Abbaszade et al. 1999; Vazquez et al. 1999; Calderon et al. 2007). ADAMTS5 is also named as aggrecanase–2 (chondroitin sulfate proteoglycanase) (Hurskainen et al. 1999). ADAMTS5 causes the functional and structural changes in ECM by cleavage of the proteoglycans such as aggrecan, versican and brevican (Stanton et al. 2005; McCulloch et al. 2009). Kumar et al. (2012) have shown that anti-angiogenetic effect of ADAMTS5 by inhibiting angiogenetic factors such as vascular endothelial growth factor (VEGF), placental growth factor (PlGF), and platelet-derived endothelial growth factor (PDECGF) (Blumer et al. 2013). Daniel et al. demonstrated the blockage of glucose uptake by ADAMTS5 in the cultures of adipose tissue-derived stromal cells (ADSC) and epiphyseal chondrocytes of knock-out mice; resulting in inhibition of aggrecan and versican synthesis and degradation of the intracellular matrix (Daniel et al. 2015).
Investigational drugs for the treatment of osteoarthritis, an update on recent developments
Published in Expert Opinion on Investigational Drugs, 2018
Zhaohua Zhu, Jia Li, Guangfeng Ruan, Guoliang Wang, Cibo Huang, Changhai Ding
ADAMTS-5 (aggrecanase-2) is the predominant member of the ADAMTS family in mice models of degenerative joint disease or OA, but its effect in humans is less clear [73]. ADAMTS-4 (aggrecanase-1) is likely to be a significant player [74]. CRB0017, a chimeric murine/human IgG4 mAb against a single domain of ADAMTS-5, was reported to dose-dependently modify OA disease progression after 3 months’ treatment, by reducing cartilage breakdown as assessed histologically in mice [75,76]. GSK2394002 was developed as a fully humanized ADAMTS-5 selective mAb (12F4.1H7) and reported to have structural-modifying and pain-relieving effect in mouse OA models [73,77]. Neutralizing antibody to both ADAMTS-4 and ADAMTS-5 has also been developed and reported to inhibit aggrecanase activity at molecular and cellular levels [78]. These results suggest anti-ADAMTS mAbs have beneficial effects on disease progression of OA in the animal model, but the safety and tolerability are needed to be investigated before trials in humans. AGG-523 is the only selective oral inhibitor of ADAMTS-4 and ADAMTS-5 that has entered phase I studies in humans (NCT00454298, NCT00427687) but the trials were suspended for unknown reasons. Clinical trials are urgently required to prove safety and efficacy of ADAMTS inhibitors in OA patients.