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

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Abstract

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.

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Abbreviations

FXIIIA:

Factor XIIIA

IL-1β:

Interleukin-1beta

TGF-β1:

Transforming growth factor-β1

TGs:

Transglutaminases

TG2:

Transglutaminase-2

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Acknowledgments

The authors are grateful to Dr. A. Ferlosio for his collaboration and L. Santangelo, S. Cappelli and A. Colantoni for their technical assistance. This study was partially financed by Prof. Orlandi’s and Prof. Tarantino’s 2007 Grants for Research from Tor Vergata University of Rome, Italy.

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Authors and Affiliations

  1. Anatomic Pathology, Department of Biopathology, University of Rome “Tor Vergata” School of Medicine, Via Montpellier, 00133, Rome, Italy

    A. Orlandi, A. Di Lascio & L. G. Spagnoli

  2. Department of Orthopaedics and Traumatology, University of Rome “Tor Vergata” School of Medicine, Viale Oxford 81, 00133, Rome, Italy

    F. Oliva, G. Taurisano & U. Tarantino

  3. Experimental Medicine and Biochemical Sciences, University of Rome “Tor Vergata” School of Medicine, Via Montpellier, Rome, Italy

    E. Candi & G. Melino

Authors
  1. A. Orlandi
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  2. F. Oliva
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  3. G. Taurisano
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  4. E. Candi
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  5. A. Di Lascio
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  6. G. Melino
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  7. L. G. Spagnoli
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  8. U. Tarantino
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Correspondence to A. Orlandi.

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Orlandi, A., Oliva, F., Taurisano, G. et al. Transglutaminase-2 differently regulates cartilage destruction and osteophyte formation in a surgical model of osteoarthritis. Amino Acids 36, 755–763 (2009). https://doi.org/10.1007/s00726-008-0129-3

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  • DOI: https://doi.org/10.1007/s00726-008-0129-3

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