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Osteoarthritis Cartilage. 2014 Feb;22(2):259-63. doi: 10.1016/j.joca.2013.12.001. Epub 2013 Dec 12.

O-linked N-acetylglucosamine (O-GlcNAc) protein modification is increased in the cartilage of patients with knee osteoarthritis.

Author information

1
Bone and Joint Research Unit, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Madrid, Spain.
2
Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
3
Donation Unit, Transplant Services Foundation, Hospital Clinic, Barcelona, Spain.
4
Bone and Joint Research Unit, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Madrid, Spain. Electronic address: rlargo@fjd.es.

Abstract

OBJECTIVE:

There is increasing evidence that the addition of O-linked N-acetylglucosamine (O-GlcNAc) to proteins plays an important role in cell signaling pathways. In chondrocytes, accumulation of O-GlcNAc-modified proteins induces hypertrophic differentiation. Osteoarthritis (OA) is characterized by cartilage degradation, and hypertrophic-like changes in hyaline chondrocytes. However, the mechanisms responsible for these changes have not been described. Our aim was to study whether O-GlcNAcylation and the enzymes responsible for this modification are dysregulated in the cartilage of patients with knee OA and whether interleukin-1 could induce these modifications in cultured human OA chondrocytes (HOC).

DESIGN:

Human cartilage was obtained from patients with knee OA and from age and sex-matched healthy donors. HOC were cultured and stimulated with the catabolic cytokine IL-1α. Global protein O-GlcNAcylation and the synthesis of the key enzymes responsible for this modification, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), were assessed by western blot.

RESULTS:

OA was associated with a 4-fold increase in the global O-GlcNAcylation in the cartilage. OA cartilage showed a re-distribution of the OGT and OGA isoforms, with a net increase in the presence of both enzymes, in comparison to healthy cartilage. In HOC, IL-1α stimulation rapidly increased O-GlcNAcylation and OGT and OGA synthesis.

CONCLUSIONS:

Our results indicate that a proinflammatory milieu could favor the accumulation of O-GlcNAcylated proteins in OA cartilage, together with the dysregulation of the enzymes responsible for this modification. The increase in O-GlcNAcylation could be responsible, at least partially, for the re-expression of hypertrophic differentiation markers that have been observed in OA.

KEYWORDS:

Cartilage; Chondrocytes; Glycosylation; Hypertrophic differentiation; O-GlcNAcylation

PMID:
24333294
DOI:
10.1016/j.joca.2013.12.001
[Indexed for MEDLINE]
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