title: Transglutaminase 2 in cartilage homoeostasis: novel links with inflammatory osteoarthritis.
abstract: Transglutaminase 2 (TG2) is highly expressed during chondrocyte maturation and contributes to the formation of a mineralised scaffold by introducing crosslinks between extracellular matrix (ECM) proteins. In healthy cartilage, TG2 stabilises integrity of ECM and likely influences cartilage stiffness and mechanistic properties. At the same time, the abnormal accumulation of TG2 in the ECM promotes chondrocyte hypertrophy and cartilage calcification, which might be an important aspect of osteoarthritis (OA) initiation. Although excessive joint loading and injuries are one of the main causes leading to OA development, it is now being recognised that the presence of inflammatory mediators accelerates OA progression. Inflammatory signalling is known to stimulate the extracellular TG2 activity in cartilage and promote TG2-catalysed crosslinking of molecules that promote chondrocyte osteoarthritic differentiation. It is, however, unclear whether TG2 activity aims to resolve or aggravate damages within the arthritic joint. Better understanding of the complex signalling pathways linking inflammation with TG2 activities is needed to identify the role of TG2 in OA and to define possible avenues for therapeutic interventions.
authors: Matrix Biology and Tissue Repair Research Unit, Oral and Biomedical Sciences, College of Biomedical and Life Sciences, School of Dentistry, Cardiff University, Heath Park, Cardiff, CF14 4XY, UK. adamczykm@cardiff.ac.uk.|Academic Unit of Bone Biology, Department of Oncology and Metabolism, Mellanby Centre For Bone Research, Medical School, The University of Sheffield, Beech Hill Road, Sheffield, S10 2RX, UK. adamczykm@cardiff.ac.uk.
authors: M
authors: 0000-0002-7405-5157
authors: M
authors: Adamczyk
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D002454:Cell Differentiation; D019902:Chondrocytes / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D020219:Chondrogenesis / Q000235:genetics / Q000276:immunology; D018450:Disease Progression; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000276:immunology; D019204:GTP-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D005786:Gene Expression Regulation; D006706:Homeostasis / Q000276:immunology*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D010003:Osteoarthritis / Q000201:enzymology* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D015398:Signal Transduction; D011503:Transglutaminases / Q000172:deficiency / Q000235:genetics / Q000276:immunology*
chemical_list: D016326:Extracellular Matrix Proteins; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins
keywords: Cartilage; Chondrocyte hypertrophy; Inflammation; Osteoarthritis; Transglutaminase