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

• Published in: Amino acids 2009-04, Vol.36 (4), p.755-763
• Main Authors: Orlandi, A, Oliva, F, Taurisano, G, Candi, E, Di Lascio, A, Melino, G, Spagnoli, L. G, Tarantino, U
• Format: Article
• Language: English
• Subjects: Analytical Chemistry; Animals; Arthritis; Biochemical Engineering; Biochemistry; Biomedical and Life Sciences; Cartilage; Cartilage - enzymology; Cartilage - metabolism; Cartilage - pathology; Disease Models, Animal; Female; GTP-Binding Proteins - biosynthesis; GTP-Binding Proteins - metabolism; Humans; Life Sciences; Male; Mice; Mice, Knockout; Neurobiology; Original Article; Osteoarthritis - enzymology; Osteoarthritis - metabolism; Osteoarthritis - surgery; Osteophyte - enzymology; Osteophyte - metabolism; Osteophyte - pathology; Proteomics; Rodents; Transforming Growth Factor beta1 - biosynthesis; Transglutaminases - biosynthesis; Transglutaminases - metabolism
• ISSN: 0939-4451; 1438-2199
• DOI: 10.1007/s00726-008-0129-3

Osteoarthritis is a progressive joint disease characterized by cartilage degradation and bone remodeling. Transglutaminases catalyze a calcium-dependent transamidation reaction that produces covalent cross-linking of available substrate glutamine residues and modifies the extracellular matrix. Increased transglutaminases-mediated activity is reported in osteoarthritis, but the relative contribution of transglutaminases-2 (TG2) is uncertain. We describe TG2 expression in human femoral osteoarthritis and in wild-type and homozygous TG2 knockout mice after surgically-induced knee joint instability. Increased TG2 levels were observed in human and wild-type murine osteoarthritic cartilage compared to the respective controls. Histomorphometrical but not X-ray investigation documented in osteoarthritic TG2 knockout mice reduced cartilage destruction and an increased osteophyte formation compared to wild-type mice. These differences were associated with increased TGFβ-1 expression. In addition to confirming its important role in osteoarthritis development, our results demonstrated that TG2 expression differently influences cartilage destruction and bone remodeling, suggesting new targeted TG2-related therapeutic strategies.