Syndecans in cartilage breakdown and synovial inflammation

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.