Anatomy and Physiology

The Function of Proteoglycan Molecules in the Matrix of Cartilage

Cartilage resilience relies on its ability to retain water. This is achieved by a unique molecular architecture that forms a durable, shock-absorbing gel.

Cartilage is a smooth, durable tissue found in joints, the nose, and ears, where it provides support and facilitates movement. The properties of cartilage come from the specialized, gel-like substance surrounding its cells, known as the extracellular matrix. This matrix is responsible for the strength and flexibility of the tissue.

The Composition of the Cartilage Matrix

The extracellular matrix (ECM) is the non-cellular part of cartilage providing structural support. It is composed of two main components. The first is a network of collagen fibers that provides tensile strength and acts as a framework, much like steel bars in concrete. This network gives cartilage its shape and resistance to tearing.

The spaces within this collagen framework are filled by the second component: large molecules forming the ground substance. These molecules create a dense, hydrated gel between the collagen fibers. The interaction between the collagen and the ground substance gives cartilage its mechanical properties and ability to function under pressure.

The Molecular Architecture of Proteoglycans

The primary molecules in the ground substance are proteoglycans. A single proteoglycan has a central core protein with many long sugar chains, called glycosaminoglycans (GAGs), extending from it. This structure resembles a bottle brush, with the core protein as the wire and GAGs as the bristles. The most common GAGs in cartilage are chondroitin sulfate and keratan sulfate.

The GAG chains have strong negative electrical charges from sulfate and uronic acid groups. In the cartilage matrix, many of these “bottle brush” units, a proteoglycan called aggrecan, attach to a long sugar molecule known as hyaluronic acid. This assembly creates a massive structure called a proteoglycan aggregate, which can contain up to 50 aggrecan monomers.

How Proteoglycans Create a Resilient Cushion

The dense concentration of negative charges on the GAG chains enables their function as shock absorbers. These charges attract and trap a large volume of water, causing the matrix to swell and become highly hydrated. This generates a high osmotic pressure within the tissue, which is contained by the collagen network. The trapped water makes cartilage a resilient cushion.

When cartilage is under compressive force from walking or jumping, some water is squeezed out of the matrix. The negatively charged proteoglycans resist this compression and water loss. When the force is removed, these charges draw water back into the matrix, restoring its original volume. This rapid recovery allows cartilage to withstand repetitive stress and provides for frictionless joint movement.

Proteoglycan Loss in Cartilage Breakdown

Cartilage degradation, a feature of conditions like osteoarthritis, involves the breakdown of this system. Certain enzymes become overactive within the matrix. Two primary classes, aggrecanases and matrix metalloproteinases (MMPs), specifically target and break down the large proteoglycan molecules, which is a central event in cartilage damage.

The degradation of aggrecan severely impacts the cartilage matrix. As enzymes cleave the core protein, GAG chains are lost, and the matrix’s ability to retain water diminishes. Without its high water content, the cartilage loses osmotic pressure, softens, and thins. This compromises its shock-absorbing capacity, leading to increased stress on the collagen and underlying bone, resulting in joint pain and stiffness.

The Natural Cycle of Proteoglycan Renewal

Despite its seemingly inert nature, cartilage is a living tissue that undergoes a slow process of maintenance and renewal. Embedded within the matrix are specialized cells called chondrocytes, which make up only about 5% of the cartilage volume. These cells are responsible for the health of the surrounding matrix.

Chondrocytes synthesize new proteoglycan and collagen molecules while also directing their controlled breakdown and removal. In a healthy state, this process of synthesis and degradation exists in a balanced equilibrium. This balance ensures the matrix remains structurally sound and functional over time.

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