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Transglutaminase 2 is a marker of chondrocyte hypertrophy and osteoarthritis severity in the Hartley guinea pig model of knee OA.

Publication ,  Journal Article
Huebner, JL; Johnson, KA; Kraus, VB; Terkeltaub, RA
Published in: Osteoarthritis Cartilage
August 2009

OBJECTIVE: The transglutaminase (TG) isoenzyme TG2, which catalyzes protein cross-linking via transamidation, influences healing phenotype in multiple forms of tissue injury. Moreover, TG2 knockout suppresses cartilage destruction but promotes osteophyte formation in instability-induced mouse knee osteoarthritis (OA). TG2 is marker of growth plate chondrocyte hypertrophy. Moreover, TG2 secreted by chondrocytes acts in part by promoting chondrocyte maturation to hypertrophy, a differentiation state linked with MMP-13 expression and disease progression in OA. Moreover, glucosamine, which is currently under investigation as an OA therapy, binds and inhibits TG2. Here, we examined TG2 as a potential marker of cartilage hypertrophy in the spontaneous guinea pig model of OA. METHODS: Synovial fluid ELISA and cartilage Immunohistochemistry and quantitative Reverse transcription-polymerase chain reaction (RT-PCR), were used to examine TG2 expression and TG transamidation-catalyzed isopeptide bonds. RESULTS: TG isopeptide bonds and TG2 were most abundant in articular cartilage in early knee OA. TG2 expression was robust at sites of early but not established osteophytes. Synovial fluid TG2 correlated with knee OA total histological score (r=0.47, P=0.01), as did medial tibial plateau cartilage TG2 mRNA (r=1.0, P=0.003). At 12 months of age, medial tibial plateau cartilage TG2 mRNA expression rose markedly in association with elevated type X collagen, as well as ADAMTS-5, and MMP-13 expression, changes not shared in age-matched Strain 13 guinea pigs that are less susceptible to knee OA. CONCLUSION: Hartley guinea pig knee TG2 expression associates with enhanced articular chondrocyte hypertrophy and is a biomarker of OA severity.

Duke Scholars

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Published In

Osteoarthritis Cartilage

DOI

EISSN

1522-9653

Publication Date

August 2009

Volume

17

Issue

8

Start / End Page

1056 / 1064

Location

England

Related Subject Headings

  • Transglutaminases
  • Severity of Illness Index
  • Protein Glutamine gamma Glutamyltransferase 2
  • Osteoarthritis, Knee
  • Immunohistochemistry
  • Guinea Pigs
  • Gene Expression
  • GTP-Binding Proteins
  • Chondrocytes
  • Cartilage, Articular
 

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Huebner, J. L., Johnson, K. A., Kraus, V. B., & Terkeltaub, R. A. (2009). Transglutaminase 2 is a marker of chondrocyte hypertrophy and osteoarthritis severity in the Hartley guinea pig model of knee OA. Osteoarthritis Cartilage, 17(8), 1056–1064. https://doi.org/10.1016/j.joca.2009.02.015
Huebner, J. L., K. A. Johnson, V. B. Kraus, and R. A. Terkeltaub. “Transglutaminase 2 is a marker of chondrocyte hypertrophy and osteoarthritis severity in the Hartley guinea pig model of knee OA.Osteoarthritis Cartilage 17, no. 8 (August 2009): 1056–64. https://doi.org/10.1016/j.joca.2009.02.015.
Huebner JL, Johnson KA, Kraus VB, Terkeltaub RA. Transglutaminase 2 is a marker of chondrocyte hypertrophy and osteoarthritis severity in the Hartley guinea pig model of knee OA. Osteoarthritis Cartilage. 2009 Aug;17(8):1056–64.
Huebner, J. L., et al. “Transglutaminase 2 is a marker of chondrocyte hypertrophy and osteoarthritis severity in the Hartley guinea pig model of knee OA.Osteoarthritis Cartilage, vol. 17, no. 8, Aug. 2009, pp. 1056–64. Pubmed, doi:10.1016/j.joca.2009.02.015.
Huebner JL, Johnson KA, Kraus VB, Terkeltaub RA. Transglutaminase 2 is a marker of chondrocyte hypertrophy and osteoarthritis severity in the Hartley guinea pig model of knee OA. Osteoarthritis Cartilage. 2009 Aug;17(8):1056–1064.
Journal cover image

Published In

Osteoarthritis Cartilage

DOI

EISSN

1522-9653

Publication Date

August 2009

Volume

17

Issue

8

Start / End Page

1056 / 1064

Location

England

Related Subject Headings

  • Transglutaminases
  • Severity of Illness Index
  • Protein Glutamine gamma Glutamyltransferase 2
  • Osteoarthritis, Knee
  • Immunohistochemistry
  • Guinea Pigs
  • Gene Expression
  • GTP-Binding Proteins
  • Chondrocytes
  • Cartilage, Articular