Aggrecan, aging and assembly in articular cartilage

Abstract

The primary function of articular cartilage to act as a self-renewing, low frictional material that can distribute load efficiently at joints is critically dependent upon the composition and organisation of the extracellular matrix. Aggrecan is a major component of the extracellular matrix, forming high molecular weight aggregates necessary for the hydration of cartilage and to meet its weight-bearing mechanical demands. Aggregate assembly is a highly ordered process requiring the formation of a ternary complex between aggrecan, link protein and hyaluronan. There is extensive age-associated heterogeneity in the structure and molecular stoichiometry of these components in adult human articular cartilage, resulting in diverse populations of complexes with a range of stabilities that have implications for cartilage mechanobiology and integrity. Recent findings have demonstrated that aggrecan can form ligands with other matrix proteins. These findings provide new insights into mechanisms for aggregate assembly and functional protein networks in different cartilage compartments with maturation and aging.

Anti-arthritic Action Mechanisms of Natural Chondroitin Sulfate in Human Articular Chondrocytes and Synovial Fibroblasts

“…Natural chondroitin sulfates are widely used for the treatment of joint pain in the world. 10) Chondroitin sulfate (CS) is a glycosaminoglycan with polysaccharide chains composed of an alternate sequence of D-glucuronic acid and D-N-acetyl galactosamine linked by b(1→3) and b(1→4) bonds, 11) and it is widely distributed in various connective tissues; it is particularly abundant in cartilage, skin, corpus vitreum, and blood vessels. Most CS exists as the sugar chains of aggrecan in the cartilage, and its high water retaining capacity ensures proper cartilage hydration.…”

Morphology, mechanisms and pathology of musculoskeletal ageing

“…With age the size of proteoglycan aggregates decreases significantly, due to reduction in size of aggrecan molecules, shortening of glycosaminoglycan side chains and a decrease in the number of aggrecan molecules per aggregate [26,27]. These result from both altered proteoglycan synthesis (eg production of less uniform and shorter aggrecan core proteins) and increased degradation due to increased local production of aggrecanases (mainly MMPs and ADAMTs [28,29]).…”

Single-nucleotide polymorphism in the hyaluronan and proteoglycan link protein 1 (HAPLN1) gene is associated with spinal osteophyte formation and disc degeneration in Japanese women

“…HAPLN proteins stabilize the binding interaction between hyaluronan and chondroitin sulfate proteoglycans [21]. HAPLN1 is known for its role in cartilage formation, where it stabilizes the hyaluronan/aggrecan and hyaluronan/versican complexes [5,6,14,16,17]. Its importance in cartilage formation has previously been demonstrated in studies on Hapln1-deficient mice [4,29].…”