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  • Review Article
  • Published:

Syndecans in cartilage breakdown and synovial inflammation

Nature Reviews Rheumatology volume 9, pages 43–55 (2013)Cite this article

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Abstract

Syndecans are transmembrane heparan sulphate proteoglycans (HSPGs) that have gained increasing interest as regulators of a variety of tissue responses, including cartilage development and remodelling. These proteoglycans are composed of a core protein to which extracellular glycosaminoglycan (GAG) chains are attached. Through these GAG chains, syndecans can interact with a variety of extracellular matrix molecules and bind to a number of soluble mediators including morphogens, growth factors, chemokines and cytokines. The structure and post-translational modification of syndecan GAG chains seem to differ not only from cell to cell, but also during different stages of cellular differentiation, leading to a complexity of syndecan function that is unique among membrane-bound HSPGs. Unlike other membrane-bound HSPGs, syndecans contain intracellular signalling motifs that can initiate signalling mainly through protein kinase C. This Review summarizes our knowledge of the biology of syndecans and the mechanisms by which binding of molecules to syndecans exert different biological effects, particularly in the joints. On the basis of the structural and functional peculiarities of syndecans, we discuss the regulation of syndecans and their roles in the developing joint as well as during degenerative and inflammatory cartilage remodelling as understood from expression studies and functional analyses involving syndecan-deficient mice.

Key Points

  • The transmembrane heparan sulphate proteoglycans of the syndecan family have been found to regulate various cellular processes in joint development and pathology

  • The variety of syndecan functions is attributable, in part, to the highly variable structure of GAG chains and consequently to diverse syndecan–ligand interactions, as well as to the specific expression pattern of each syndecan

  • One singularity of syndecans, compared with other membrane-bound heparan sulphate proteoglycans, is the possibility of independent signal transduction owing to their having intracellular signalling domains

  • These unique features make syndecans important for cartilage development and degenerative and inflammatory joint pathology

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Figure 1: Members and structure of the syndecan family of transmembrane heparan sulphate proteoglycans.
Figure 2: Structure and assembly of the GAG side chains of syndecans.
Figure 3: Hypothetical molecular states of syndecans.
Figure 4: Fibronectin-induced integrin-dependent signalling pathways.
Figure 5: Model of SYND4-induced aggrecan cleavage in osteoarthritis.

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Acknowledgements

The authors' work is supported in part by grants from the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) and the German Federal Ministry of Education and Research (Bundesminsterium für Bildung und Forschung, BMBF).

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  1. Institute of Experimental Musculoskeletal Medicine, University Hospital Münster, Domagkstraße 3, Münster, D-48149, Germany

    Thomas Pap & Jessica Bertrand

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Pap, T., Bertrand, J. Syndecans in cartilage breakdown and synovial inflammation. Nat Rev Rheumatol 9, 43–55 (2013). https://doi.org/10.1038/nrrheum.2012.178

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