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Consequences of metabolic and oxidative modifications of cartilage tissue

Nature Reviews Rheumatology volume 11, pages 521–529 (2015)Cite this article

Subjects

Key Points

  • Diabetes, metabolic syndrome and chronic infections increase glycaemia, lipidaemia and cellular levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS)

  • Increased glycaemia, lipidaemia, ROS and RNS induce glycation, glycoxidation, carbonylation and nitrosylation of cartilage proteins

  • Biochemical changes in proteins compromise the anatomical organization of cartilage

  • Changes in the anatomical organization of cartilage compromise tissue visco-elasticity and, ultimately, the ability of cartilage to sustain pressure and its overall performance

  • Protein biochemical changes are an early event in cartilage degeneration

Abstract

A hallmark of chronic metabolic diseases, such as diabetes and metabolic syndrome, and oxidative stress, as occurs in chronic inflammatory and degenerative conditions, is the presence of extensive protein post-translational modifications, including glycation, glycoxidation, carbonylation and nitrosylation. These modifications have been detected on structural cartilage proteins in joints and intervertebral discs, where they are known to affect protein folding, induce protein aggregation and, ultimately, generate microanatomical changes in the proteoglycan–collagen network that surrounds chondrocytes. Many of these modifications have also been shown to promote oxidative cleavage as well as enzymatically-mediated matrix degradation. Overall, a general picture starts to emerge indicating that biochemical changes in proteins constitute an early event that compromises the anatomical organization and viscoelasticity of cartilage, thereby affecting its ability to sustain pressure and, ultimately, impeding its overall bio-performance.

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Figure 1: A schematic representation of articular cartilage.
Figure 2: Overview of the different mechanisms by which proteins can become carbonylated.
Figure 3: Step-by-step mechanisms by which advanced glycation end products (AGEs) are formed.
Figure 4: The effects of oxidative post-translational modifications on the structure of collagens and proteoglycans.

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  1. Department of Orthopedic Surgery, Montefiore Medical Centre, 1250 Waters Place, New York, 10467, NY, USA

    John A. Hardin & Neil Cobelli

  2. Departments of Pathology, Microbiology and Immunology and Orthopedic Surgery, Albert Einstein College of Medicine, 1300 Morris Park Avenue, New York, 10461, NY, USA

    Laura Santambrogio

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J.H. and L.S. researched the data for the article and wrote the manuscript. All authors (J.H., N.C. and L.S.) contributed substantially to discussions of the article content, and review or editing of manuscript before submission.

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Correspondence to Laura Santambrogio.

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Hardin, J., Cobelli, N. & Santambrogio, L. Consequences of metabolic and oxidative modifications of cartilage tissue. Nat Rev Rheumatol 11, 521–529 (2015). https://doi.org/10.1038/nrrheum.2015.70

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