• Home
  • Search Results
  • Transglutaminase factor XIII promotes arthritis through mechanisms linked to inflammation and bone erosion.

Transglutaminase factor XIII promotes arthritis through mechanisms linked to inflammation and bone erosion.

Blood (2014-10-23)
Harini Raghu, Carolina Cruz, Cheryl L Rewerts, Malinda D Frederick, Sherry Thornton, Eric S Mullins, Jonathan G Schoenecker, Jay L Degen, Matthew J Flick
ABSTRACT

Rheumatoid arthritis is a chronic inflammatory disease characterized by synovial hyperplasia, inflammatory cell infiltration, irreversible cartilage and bone destruction, and exuberant coagulation system activity within joint tissue. Here, we demonstrate that the coagulation transglutaminase, factor XIII (fXIII), drives arthritis pathogenesis by promoting local inflammatory and tissue degradative and remodeling events. All pathological features of collagen-induced arthritis (CIA) were significantly reduced in fXIII-deficient mice. However, the most striking difference in outcome was the preservation of cartilage and bone in fXIIIA(-/-) mice concurrent with reduced osteoclast numbers and activity. The local expression of osteoclast effectors receptor activator of nuclear factor-κB ligand (RANKL) and tartrate resistant acid phosphatase were significantly diminished in CIA-challenged and even unchallenged fXIIIA(-/-) mice relative to wild-type animals, but were similar in wild-type and fibrinogen-deficient mice. Impaired osteoclast formation in fXIIIA(-/-) mice was not due to an inherent deficiency of monocyte precursors, but it was linked to reduced RANKL-driven osteoclast formation. Furthermore, treatment of mice with the pan-transglutaminase inhibitor cystamine resulted in significantly diminished CIA pathology and local markers of osteoclastogenesis. Thus, eliminating fXIIIA limits inflammatory arthritis and protects from cartilage and bone destruction in part through mechanisms linked to reduced RANKL-mediated osteoclastogenesis. In summary, therapeutic strategies targeting fXIII activity may prove beneficial in limiting arthropathies and other degenerative bone diseases.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Collagen, Type I solution from rat tail, BioReagent, suitable for cell culture, sterile-filtered
Sigma-Aldrich
Collagen from human placenta, Bornstein and Traub Type IV, powder, BioReagent, suitable for cell culture
Sigma-Aldrich
Collagen from rat tail, Bornstein and Traub Type I, powder, BioReagent, suitable for cell culture
Sigma-Aldrich
Collagen from human placenta, Bornstein and Traub Type IV, powder
Sigma-Aldrich
Collagen from calf skin, Bornstein and Traub Type I, (0.1% solution in 0.1 M acetic acid), aseptically processed, BioReagent, suitable for cell culture
Sigma-Aldrich
Collagen from bovine achilles tendon, powder, suitable for substrate for collagenase
Sigma-Aldrich
Collagen from chicken sternal cartilage, Type II (Miller), powder, BioReagent, suitable for cell culture
Sigma-Aldrich
Cystamine dihydrochloride, 96%
Sigma-Aldrich
Collagen from calf skin, Bornstein and Traub Type I, solid, BioReagent, suitable for cell culture
Sigma-Aldrich
Collagen Type IV from human cell culture, Bornstein and Traub Type IV, 0.3 mg/mL, sterile-filtered, BioReagent, suitable for cell culture
Sigma-Aldrich
Cystamine dihydrochloride, purum, ≥98.0% (AT)
Sigma-Aldrich
Collagen from human placenta, Bornstein and Traub Type I (Sigma Type VIII), powder
Sigma-Aldrich
Collagen from calf skin, Bornstein and Traub Type I (Sigma Type III), solid
Sigma-Aldrich
Collagen from bovine nasal septum, Bornstein and Traub Type II, powder
Sigma-Aldrich
Collagen human, Bornstein and Traub Type I, acid soluble, powder, ~95% (SDS-PAGE)
Sigma-Aldrich
Collagen from human placenta, Bornstein and Traub Type III (Sigma Type X), powder
Sigma-Aldrich
Collagen from Engelbreth-Holm-Swarm murine sarcoma basement membrane, Type IV (Miller), lyophilized powder, BioReagent, suitable for cell culture
Sigma-Aldrich
Cystamine dihydrochloride, BioXtra
Sigma-Aldrich
Collagen from human placenta, Bornstein and Traub Type IV, solution, suitable for cell culture, High Performance
Sigma-Aldrich
Collagen from rat tail, Bornstein and Traub Type I (Sigma Type VII), powder
Sigma-Aldrich
Collagen from bovine tracheal cartilage, Bornstein and Traub Type II, powder
Sigma-Aldrich
Collagen from human placenta, Bornstein and Traub Type IV, powder
Sigma-Aldrich
Collagen from human placenta, Bornstein and Traub Type V (Sigma Type IX), powder
Sigma-Aldrich
Ser-Phe-Leu-Leu-Arg-Asn-Pro-Asn-Asp-Lys-Tyr-Glu-Pro-Phe, ≥97% (HPLC)
Sigma-Aldrich
Collagen from rabbit skin, Bornstein and Traub Type I, powder

Social Media

LinkedIn icon
Twitter icon
Facebook Icon
Instagram Icon

MilliporeSigma

Research. Development. Production.

We are a leading supplier to the global Life Science industry with solutions and services for research, biotechnology development and production, and pharmaceutical drug therapy development and production.

© 2021 Merck KGaA, Darmstadt, Germany and/or its affiliates. All Rights Reserved.

Reproduction of any materials from the site is strictly forbidden without permission.