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Molecular biology

GAG (glycosaminoglycan)

The sugar chains that give cartilage its strength and skin its hydration

Definition

Glycosaminoglycans (GAGs) are long, linear sugar chains built from repeating disaccharide units — a core structural component of the extracellular matrix in nearly every animal tissue. Their high density of negative charges attracts and holds water, generating an osmotic swelling pressure that, combined with collagen fibres, gives articular cartilage its resistance to compression. The main GAGs are chondroitin sulfate, keratan sulfate, heparan sulfate, dermatan sulfate and hyaluronic acid. Their decline with age is linked to cartilage degradation, dry skin and loss of tissue elasticity, which is why GAG precursors are widely used as chondroprotective supplements.

Detailed explanation

GAGs are classified as sulfated (chondroitin, keratan, heparan and dermatan sulfate) or non-sulfated (hyaluronic acid). Except for hyaluronic acid, all bind covalently to a core protein to form proteoglycans such as aggrecan, the dominant macromolecule of hyaline cartilage. A single proteoglycan can carry more than a hundred GAG chains, and many aggrecans anchor onto a hyaluronic acid filament to build giant aggregates.

The biomechanical function stems from the chemistry: ionised carboxyl and sulfate groups give GAGs a densely fixed negative charge that draws in counterions and, with them, water. This swelling pressure — restrained by the type II collagen network — lets cartilage resist loads several times body weight without collapsing.

In osteoarthritis, matrix metalloproteinases (MMPs) and aggrecanases (ADAMTS) degrade proteoglycans; chondroitin sulfate is lost and the matrix's fixed negative charge falls, reducing water retention and accelerating wear. This is why chondroitin sulfate and glucosamine — GAG precursors — are used as chondroprotectives, and hyaluronic acid is injected to restore joint viscosity. Beyond the joint, heparan sulfate regulates growth-factor signalling and dermal hyaluronic acid governs skin hydration.

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