Nat Genet
November 2024
Lysyl oxidases (LOX(L)) are enzymes that catalyze the formation of cross-links in collagen and elastin fibers during physiologic calcification of bone. However, it remains unknown whether they may promote pathologic calcification of articular cartilage, an important hallmark of debilitating arthropathies. Here, we have studied the possible roles of LOX(L) in cartilage calcification, related and not related to their cross-linking activity.
View Article and Find Full Text PDFNat Rev Rheumatol
January 2023
Pathological calcification of cartilage is a hallmark of osteoarthritis (OA). Calcification can be observed both at the cartilage surface and in its deeper layers. The formation of calcium-containing crystals, typically basic calcium phosphate (BCP) and calcium pyrophosphate dihydrate (CPP) crystals, is an active, highly regulated and complex biological process that is initiated by chondrocytes and modified by genetic factors, dysregulated mitophagy or apoptosis, inflammation and the activation of specific cellular-signalling pathways.
View Article and Find Full Text PDFObjective: To determine whether a gout polygenic risk score (PRS) is associated with age at gout onset and tophaceous disease in European, East Polynesian, and West Polynesian men and women with gout.
Methods: A 19-variant gout PRS was produced in 7 European gout cohorts (N = 4,016), 2 East Polynesian gout cohorts (N = 682), and 1 West Polynesian gout cohort (N = 490). Sex-stratified regression models were used to estimate the relationship between the PRS and age at gout onset and tophaceous disease.
Background: Cartilage damage in inflammatory arthritis is attributed to inflammatory cytokines and pannus infiltration. Activation of the coagulation system is a well known feature of arthritis, especially in rheumatoid arthritis (RA). Here we describe mechanisms by which fibrin directly mediates cartilage degeneration.
View Article and Find Full Text PDFHyperuricemia is often encountered as glomerular filtration rate decreased. It is associated with a more rapid decline of the renal function, but causality has not been demonstrated. Recent studies showed that treatment of hyperuricemia did not affect the progression in chronic kidney disease (CKD) patients.
View Article and Find Full Text PDFPathologic calcification (PC) is a painful and disabling condition whereby calcium-containing crystals deposit in tissues that do not physiologically calcify: cartilage, tendons, muscle, vessels and skin. In cartilage, compression and inflammation triggered by PC leads to cartilage degradation typical of osteoarthritis (OA). The PC process is poorly understood and treatments able to target the underlying mechanisms of the disease are lacking.
View Article and Find Full Text PDFObjective: Classification criteria for calcium pyrophosphate deposition (CPPD) disease will facilitate clinical research on this common crystalline arthritis. Our objective was to report on the first 2 phases of a 4-phase process for developing CPPD classification criteria.
Methods: CPPD classification criteria development is overseen by a 12-member steering committee.
Pathologic calcification of cartilage consists of the formation of basic calcium phosphate (BCP) and/or calcium pyrophosphate dihydrate (CPPD) containing calcium crystals in mature hyaline or articular cartilage and is associated with aging, cartilage injury and likely plays a role in accelerating the pathology of osteoarthritis (OA). The pathways regulating joint calcification, in particular cartilage calcification, are not completely understood, but inflammation and the formation of reactive oxygen species (ROS) are contributory factors. The xanthine oxidase (XO) form of xanthine oxidoreductase (XOR), the key enzyme in xanthine and uric acid metabolism, is a major cellular source of superoxide.
View Article and Find Full Text PDFObjective: To evaluate the efficacy and safety of anakinra compared to triamcinolone in the treatment of gout flares.
Methods: Patients for whom nonsteroidal antiinflammatory drugs and colchicine were not suitable treatments were enrolled in this multicenter, randomized, double-blind study with follow-up for up to 2 years. The study was designed to assess superiority of anakinra (100 or 200 mg/day for 5 days) over triamcinolone (40 mg in a single injection) for the primary end point of changed patient-assessed pain intensity in the most affected joint (scored on a visual analog scale of 0-100) from baseline to 24-72 hours.
Osteoarthritis (OA) is a progressive joint disease that is strongly associated with calcium-containing crystal formation (mineralization) by chondrocytes leading ultimately to cartilage calcification. However, this calcification process is poorly understood and treatments targeting the underlying disease mechanisms are lacking. The CD11b/CD18 integrin (Mac-1 or αMβ2), a member of the beta 2 integrin family of adhesion receptors, is critically involved in the development of several inflammatory diseases, including rheumatoid arthritis and systemic lupus erythematosus.
View Article and Find Full Text PDFBackground: Osteoarthritis (OA) is characterized by the formation and deposition of calcium-containing crystals in joint tissues, but the underlying mechanisms are poorly understood. The gasotransmitter hydrogen sulfide (HS) has been implicated in mineralization but has never been studied in OA. Here, we investigated the role of the HS-producing enzyme 3-mercaptopyruvate sulfurtransferase (3-MST) in cartilage calcification and OA development.
View Article and Find Full Text PDFObjective: The aim of this study was to examine whether serum urate-associated genetic variants are associated with early-onset gout.
Methods: Participants with gout in the Genetics of Gout in Aotearoa study with available genotyping were included (n = 1648). Early-onset gout was defined as the first presentation of gout <40 years of age.