Transglutaminase-2 differently regulates cartilage destruction and osteophyte formation in a surgical model of osteoarthritis

Orlandi, Augusto; Oliva, Francesco; Taurisano, G.; Candi, Eleonora; Lascio, Antonio Di; Melino, Gerry; Spagnoli, Luigi Giusto; Tarantino, Umberto

doi:10.1007/s00726-008-0129-3

Cited by 37 publications

(29 citation statements)

References 32 publications

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“…It is well known that articular chondrocytes undergo maturation during early OA pathogenesis, after which the characteristic maturational marker genes collagen X [28][29][30] and MMP-13 [31,32] are expressed. MMP-13 is a potent enzyme that preferentially targets type II collagen in the cartilage matrix for degradation; interestingly, MMP-13 expression has been found to be increased in human OA joints [33]. The mouse OA model expressing constitutively active MMP-13 presents with an OA-like phenotype [34,35].…”

Section: Discussionmentioning

confidence: 99%

Dual function of β-catenin in articular cartilage growth and degeneration at different stages of postnatal cartilage development

Niu

Wang

Xinghong

et al. 2011

International Orthopaedics (SICOT)

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Purpose The objective of this study was to determine the role of β-catenin in normal postnatal articular cartilage growth and degeneration. Methods We investigated β-catenin gene and protein expression in hip cartilage cells of normal Wistar rats at two, four, six and eight weeks of age by using reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. Primary articular chondrocytes from eight week old rats were cultured and treated with LiCl for activation of β-catenin. Collagen X and matrix metalloproteinase 13 (MMP-13) were detected by quantitative RT-PCR and immunofluorescence. A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4 and 5 were detected by quantitative RT-PCR, and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) was used for detecting cell apoptosis. Results The highest levels of β-catenin expressions were detected in two week old rats, after which a steady decline was observed over the remaining period of observation (p< 0.05). When primary articular chondrocytes from eight week old rats were treated with LiCl, β-catenin mRNA and protein were induced (p<0.05). Moreover, LiCl-activated β-catenin in chondrocytes was associated with significant concomitant increases in mRNA expression of collagen X and the MMP-13 encoding collagenase 3. Significantly increased mRNA expression of ADAMTS-5 was also seen in primary chondrocytes from eight week old rats after LiCl treatment (p<0.05). The effect was specific to ADAMTS-5 since ADAMTS-4, which has similar proteolytic activity but different aggrecanase activity, was unaffected. Finally, TUNEL staining revealed that LiCl-activated β-catenin signalling led to increased cell apoptotic events in chondrocytes (p<0.05). Conclusions Our findings suggest that normal spatiotemporal patterns and degrees of Wnt/β-catenin signalling are needed to maintain postnatal articular cartilage growth and function. In the early stages of cartilage development, activation of β-catenin signalling is necessary for articular cartilage growth, while in adult cartilage it leads to degeneration and osteoarthritic-like chondrocytes.

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Section: Discussionmentioning

confidence: 99%

Dual function of β-catenin in articular cartilage growth and degeneration at different stages of postnatal cartilage development

Niu

Wang

Xinghong

et al. 2011

International Orthopaedics (SICOT)

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“…This accelerates chondrocyte hypertrophy and matrix catabolism via receptor for advanced glycation end products (RAGE) signaling (58). In a surgically induced knee joint instability model of osteoarthritis, mixed strain (SVJ129-C57BL/6) TG2 Ϫ/Ϫ mice had reduced cartilage destruction and increased osteophyte formation relative to wild-type littermates (214). This phenotype was associated with increased expression of TGF-␤1, which promotes osteophyte formation (30), in the osteoarthritic tissues of the TG2 Ϫ/Ϫ mice compared with TG2 ϩ/ϩ mice (214).…”

Section: H Tg2 Fxiii-a Bone and Osteoarthritismentioning

confidence: 99%

“…In a surgically induced knee joint instability model of osteoarthritis, mixed strain (SVJ129-C57BL/6) TG2 Ϫ/Ϫ mice had reduced cartilage destruction and increased osteophyte formation relative to wild-type littermates (214). This phenotype was associated with increased expression of TGF-␤1, which promotes osteophyte formation (30), in the osteoarthritic tissues of the TG2 Ϫ/Ϫ mice compared with TG2 ϩ/ϩ mice (214). Together, these studies point to a role for TG2 in modulating cartilage repair and stability in response to certain pathological stressors and identify TG2 as a potential target for therapeutic intervention in osteoarthritis.…”

Section: H Tg2 Fxiii-a Bone and Osteoarthritismentioning

confidence: 99%

Transglutaminases and Disease: Lessons From Genetically Engineered Mouse Models and Inherited Disorders

Iismaa¹,

Mearns²,

Lóránd³

et al. 2009

Physiological Reviews

305

336

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The human transglutaminase (TG) family consists of a structural protein, protein 4.2, that lacks catalytic activity, and eight zymogens/enzymes, designated factor XIII-A (FXIII-A) and TG1-7, that catalyze three types of posttranslational modification reactions: transamidation, esterification, and hydrolysis. These reactions are essential for biological processes such as blood coagulation, skin barrier formation, and extracellular matrix assembly but can also contribute to the pathophysiology of various inflammatory, autoimmune, and degenerative conditions. Some members of the TG family, for example, TG2, can participate in biological processes through actions unrelated to transamidase catalytic activity. We present here a comprehensive review of recent insights into the physiology and pathophysiology of TG family members that have come from studies of genetically engineered mouse models and/or inherited disorders. The review focuses on FXIII-A, TG1, TG2, TG5, and protein 4.2, as mice deficient in TG3, TG4, TG6, or TG7 have not yet been reported, nor have mutations in these proteins been linked to human disease.

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“…In chronic inflammatory diseases like: rheumatoid arthritis, osteoarthritis by activating TGF-β. It is considered as a biomarker of osteoarthritis and regulator of cartilage destruction and osteophyte and invadopodia formation [12][13][14]. Most recently TG2 was found to be essential for adherence of porphyromonas gingivalis (an environmental inducer of rheumatoid arthritis) to host cells [15].…”

mentioning

confidence: 99%

“…Just to enumerate some of them: elliptocytosis, EhlersDanlos syndrome type III, harlequin ichthyosis, ichthyosis bullosa, glucagon deficiency, pachyonychia congenital, α ketoglutarate dehydrogenase deficiency, phosphoglycerate dehydrogenase deficiency, alkaptinuria, Huntington's, recessive dystrophic epidermolysis bullosa, and cystic fibrosis [20]. 2,6,7,11,[13][14][15]17,19] Genetic Elliptocytosis, Ehlers-Danlos syndrome type III, harlequin ichthyosis, ichthyosis bullosa, glucagon deficiency, pachyonychia congenital, α ketoglutarate dehydrogenase deficiency, phosphoglycerate dehydrogenase deficiency, alkaptinuria, Huntington's, recessive dystrophic epidermolysis bullosa, cystic fibrosis [1,20] …”

mentioning

confidence: 99%

Transglutaminase 2 and Anti Transglutaminase 2 Autoantibodies in Celiac Disease and Beyond: TG2 Double-Edged Sword: Gut and Extraintestinal Involvement

Lerner¹,

Neidhöfer²

2015

Immunome Res

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Transglutaminase2 is a pleiotropic enzyme expressed ubiquitously and abundantly. It has been implicated in a variety of physiological processes, such as growth, differentiation, migration, signaling, cytoprotection, cell death and survival, wound healing, angiogenesis, inflammation, apoptosis and autophagy. It operates intracellularly in multiple organelles, extracellularly and on cell surface. Apart from catalyzing post-translational modifications of proteins, by deamidation and cross-linking, it exercises G-protein, isomerase and kinase activities and non-enzymatic biological functions. Aberrant activation or deregulation of its functions is involved in numerous human disease. The most known one is celiac disease, but the present review will expand on extraintestinal entities. It plays a role in inflammatory, degenerative-age related, neurodegenerative, malignant, metabolic and hormonal, autoimmune and genetic conditions. Increased knowledge of its structure, functions and regulation in homeostatic phase, open the opportunity to design new therapeutic strategies to inhibit its malfunction in pathological situations. Characteristics of Physiologic Transglutaminase2 (TG2)Transglutaminase (Enzyme Commission [EC] no. 2.3.2.13, OMIN * 190196), i.e., protein-glutamine γ-glutamyltransferase, belongs to the class of transferases. It catalyzes the formation of an isopeptide bond between the group of γ-carboxamides of glutamine residues (donor) and the first-order ε-amine groups of different compounds, for instance, proteins (acceptors of an acyl residue). The human TG2 gene is localized to chromosome 20q11-12, the protein is made up of 687 amino acids and it is called also tissue TG. It is the most abundant and most studied of the nine members of the TG enzyme family [1].Three reactions are catalyzed by transglutaminase: an acyl-transfer reaction, a crosslinking reaction between Gln and Lys residues of proteins or peptides (transamidation), and deamidation. If lysine is the acceptor of an acyl group, then a protein molecule is enriched with this amino acid. The transfer of an acyl group onto a lysine residue bound in the polypeptide chain induces the process of crosslinking. In addition, transglutaminase catalyzes the reaction of deamination if there is an absence of free amine groups. The reactions catalyzed by this enzyme result in significant post translational modification and changes in the physical and chemical properties of proteins, such as modifications in the viscosity, thermal stability, elasticity, and resilience [2]. Beside the primary TG enzymes' activity of catalyzing the calciumdependent post translational modifications, it can also bind and hydrolyze GTP, exhibit protein disulphide isomerase and kinase activities, independently of calcium and mediates trans-membrane signal transduction and interactions between cell surface proteins and the extracellular matrix. It can interact with a number of cell surface proteins, in a non-enzymatic way, taking part in cell adhesion passways and extracellul...

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Transglutaminase-2 differently regulates cartilage destruction and osteophyte formation in a surgical model of osteoarthritis

Cited by 37 publications

References 32 publications

Dual function of β-catenin in articular cartilage growth and degeneration at different stages of postnatal cartilage development

Dual function of β-catenin in articular cartilage growth and degeneration at different stages of postnatal cartilage development

Transglutaminases and Disease: Lessons From Genetically Engineered Mouse Models and Inherited Disorders

Transglutaminase 2 and Anti Transglutaminase 2 Autoantibodies in Celiac Disease and Beyond: TG2 Double-Edged Sword: Gut and Extraintestinal Involvement

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