Transglutaminase-2 differently regulates cartilage destruction and osteophyte formation in a surgical model of osteoarthritis.
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 TGFbeta-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.
Orlandi
A
A
Anatomic Pathology, Department of Biopathology, University of Rome Tor Vergata, School of Medicine, Via Montpellier, 00133, Rome, Italy. orlandi@uniroma2.it
Oliva
F
F
Taurisano
G
G
Candi
E
E
Di Lascio
A
A
Melino
G
G
Spagnoli
L G
LG
Tarantino
U
U
D000818:Animals; D002356:Cartilage / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D019204:GTP-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010003:Osteoarthritis / Q000201:enzymology / Q000378:metabolism* / Q000601:surgery*; D054850:Osteophyte / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis; D011503:Transglutaminases / Q000096:biosynthesis / Q000378:metabolism*
D053773:Transforming Growth Factor beta1; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins