Structure and function of aggrecan

Abstract

Aggrecan is the major proteoglycan in the articular cartilage. This molecule is important in the proper functioning of articular cartilage because it provides a hydrated gel structure (via its interaction with hyaluronan and link protein) that endows the cartilage with load-bearing properties. It is also crucial in chondroskeletal morphogenesis during development. Aggrecan is a multimodular molecule expressed by chondrocytes. Its core protein is composed of three globular domains (G1, G2, and G3) and a large extended region (CS) between G2 and G3 for glycosaminoglycan chain attachment. G1 comprises the amino terminus of the core protein. This domain has the same structural motif as link protein. Functionally, the G1 domain interacts with hyaluronan acid and link protein, forming stable ternary complexes in the extracellular matrix. G2 is homologous to the tandem repeats of G1 and of link protein and is involved in product processing. G3 makes up the carboxyl terminus of the core protein. It enhances glycosaminoglycan modification and product secretion. Aggrecan plays an important role in mediating chondrocyte-chondrocyte and chondrocyte-matrix interactions through its ability to bind hyaluronan.

The interaction of versican with its binding partners

“…The characteristic features of hyalectans, also termed lecticans, are their similar globular structures at both N-and C-termini [4,16], and their lectin-like activity [17]. This sub-group of proteoglycans contains multiple domains and mediates a variety of cell activities [10,[18][19][20][21][22].…”

The role of proteases in pathologies of the synovial joint

“…Type II collagen fibrils confer tensile strength to the tissue and form a network that gives the tissue structure. Aggrecan binds hyaluronan to form large, highly anionic aggregates that attract water and, when restrained within the collagen framework, provide resistance to compression (Hardingham, Fosang, & Dudhia, 1994;Kiani, Chen, Wu, Yee, & Yang, 2002).…”

“…Aggrecan possesses approximately 100 chondroitin sulphate chains of around 20 kDa in size and up to 60 keratan sulphate chains of 5-15 kDa covalently attached to its protein core predominantly between the second and third of three globular domains (Hardingham et al, 1994;Kiani et al, 2002). The large number of negative groups associated with the sulphates and hydroxyls of the chondroitin sulphate chains attract water molecules that are functionally important in conferring compressive resistance to the tissue (Hardingham et al, 1994;Kiani et al, 2002).…”

“…The large number of negative groups associated with the sulphates and hydroxyls of the chondroitin sulphate chains attract water molecules that are functionally important in conferring compressive resistance to the tissue (Hardingham et al, 1994;Kiani et al, 2002). The N-terminal globular domain of aggrecan mediates the interaction between aggrecan and hyaluronan, an interaction that is stabilised by link protein (Day, 1999).…”

In VitroEvaluation of a Novel Non-Mulberry Silk Scaffold for Use in Tendon Regeneration

“…50 Chondrocyte and osteoblast genes were also assessed as tenocytes tend to transdifferentiate into such cell types, one of the pathological causes of tendinopathy. 51 The assessed genes were collagen type II (Rn01637087_m1), the major structural collagen of cartilage 52 ; aggrecan (Rn00573424_m1), the major glycoprotein in cartilage and a marker of chondrogenesis 53 ; Sp7 (osterix) (Rn02769744_s1), a transcription factor and marker of osteoblast differentiation 54 ; and bone sialoprotein (Rn00561414_m1), a marker of late osteoblast differentiation. 55 Monocyte-derived dendritic cell activation assays PBMCs were purified by gradient density purification from healthy human volunteer blood.…”