Reversible skeletal abnormalities in γ-glutamyl transpeptidase-deficient mice

Regis Levasseur, Roberto Barrios, Florent Elefteriou, Donald A. Glass, Michael W. Lieberman, Gerard Karsenty

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

γ-Glutamyl transpeptidase (GGT) is a widely distributed ectopeptidase responsible for the degradation of glutathione in the γ-glutamyl cycle. This cycle is implicated in the metabolism of cysteine, and absence of GGT causes a severe intracellular decrease in this amino acid. GGT-deficient (GGT-/-) mice have multiple metabolic abnormalities and are dwarf. We show here that this latter phenotype is due to a decreased of the growth plate cartilage total height resulting from a proliferative defect of chondrocytes. In addition, analysis of vertebrae and tibiae of GGT-/- mice revealed a severe osteopenia. Histomorphometric studies showed that this low bone mass phenotype results from an increased osteoclast number and activity as well as from a marked decrease in osteoblast activity. Interestingly, neither osteoblasts, osteoclasts, nor chondrocytes express GGT, suggesting that the observed defects are secondary to other abnormalities. N-acetylcysteine supplementation has been shown to reverse the metabolic abnormalities of the GGT-/- mice and in particular to restore the level of IGF-1 and sex steroids in these mice. Consistent with these previous observations, N-acetylcysteine treatment of GGT-/- mice ameliorates their skeletal abnormalities by normalizing chondrocytes proliferation and osteoblastic function. In contrast, resorbtion parameters are only partially normalized in GGT-/- N-acetylcysteine-treated mice, suggesting that GGT regulates osteoclast biology at least partly independently of these hormones. These results establish the importance of cysteine metabolism for the regulation of bone remodeling and longitudinal growth.

Original languageEnglish (US)
Pages (from-to)2761-2764
Number of pages4
JournalEndocrinology
Volume144
Issue number7
DOIs
StatePublished - Jul 1 2003

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gamma-Glutamyltransferase
Acetylcysteine
Osteoclasts
Chondrocytes
Osteoblasts
Cysteine
Multiple Abnormalities
Growth Plate
Bone Remodeling
Metabolic Bone Diseases
Tibia
Insulin-Like Growth Factor I
Cartilage
Glutathione
Spine
Steroids
Hormones
Phenotype
Amino Acids
Bone and Bones

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Levasseur, R., Barrios, R., Elefteriou, F., Glass, D. A., Lieberman, M. W., & Karsenty, G. (2003). Reversible skeletal abnormalities in γ-glutamyl transpeptidase-deficient mice. Endocrinology, 144(7), 2761-2764. https://doi.org/10.1210/en.2002-0071

Reversible skeletal abnormalities in γ-glutamyl transpeptidase-deficient mice. / Levasseur, Regis; Barrios, Roberto; Elefteriou, Florent; Glass, Donald A.; Lieberman, Michael W.; Karsenty, Gerard.

In: Endocrinology, Vol. 144, No. 7, 01.07.2003, p. 2761-2764.

Research output: Contribution to journalArticle

Levasseur, R, Barrios, R, Elefteriou, F, Glass, DA, Lieberman, MW & Karsenty, G 2003, 'Reversible skeletal abnormalities in γ-glutamyl transpeptidase-deficient mice', Endocrinology, vol. 144, no. 7, pp. 2761-2764. https://doi.org/10.1210/en.2002-0071
Levasseur R, Barrios R, Elefteriou F, Glass DA, Lieberman MW, Karsenty G. Reversible skeletal abnormalities in γ-glutamyl transpeptidase-deficient mice. Endocrinology. 2003 Jul 1;144(7):2761-2764. https://doi.org/10.1210/en.2002-0071
Levasseur, Regis ; Barrios, Roberto ; Elefteriou, Florent ; Glass, Donald A. ; Lieberman, Michael W. ; Karsenty, Gerard. / Reversible skeletal abnormalities in γ-glutamyl transpeptidase-deficient mice. In: Endocrinology. 2003 ; Vol. 144, No. 7. pp. 2761-2764.
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