Arthritis. As time goes by, many of the people we know and love will begin to experience the symptoms: sore joints, swelling, inflammation, stiffness, impaired mobility and pain. It’s one of those conditions that is a part of life and the general ‘wear and tear’ that goes hand-in-hand with aging. As we get older, our joints, and the layers of cartilage that prevent our bones from rubbing directly against one another, begin to show the signs of constant use and abuse over a lifetime. They wear thin and deteriorate.
Australian research has shown that arthritis affects approximately 16.5% of people, with 5% of the general population taking prescribed arthritis medication of some kind. In addition to prescription anti-inflammatory and other arthritis drugs, adjunctive and alternative treatments have found great favour over the past several years, with many individuals taking a combination of preparations in order to prevent or treat their arthritis. Consequently, words such as omega-3, glucosamine and chondroitin are now readily associated with arthritis by most. But why?
The following article investigates the reasoning and evidence supporting the use of chondroitin for the treatment of arthritis…
Arthritis at a Glance…
Wherever two bones articulate with one another in the body, they are generally prevented from rubbing directly against each other by a thin protective layer of cartilage around their heads. This largely collagen-composed layer helps to ensure that bones glide smoothly across one another when they come into contact, a process which is further lubricated by synovial fluid in the knee joint.
Cartilage and other connective tissues are heavily steeped in extracellular matrix – the ‘filler’ substance in between cells in animal organisms. As time goes on and people age, the water content in bone cartilage tends to decrease due to a gradual reduction in proteoglycan levels in the extracellular matrix, leaving the collagen fibres within the cartilage more open to degradation. As the water and collagen within the cartilage deteriorates, the cartilage itself becomes less resilient, losing its elastic properties and allowing bone to grind against bone. This is one of the primary causes for inflammation in the most common form of arthritis: osteoarthritis.
The aetiology of rheumatoid and other forms of arthritis differ, but the net effects are often the same: degraded cartilage around the joints, resulting in considerable pain, swelling and decreased movement.
Proteoglycans
Proteoglycans are a key component of the extracellular matrix, where they tend to form large complexes, binding to other proteoglycans, hyaluronic acid and fibrous matrix proteins such as collagen. They are involved in binding substances such as sodium, potassium, calcium and water, as well as controlling the movement of molecules through the matrix. Proteoglycans can therefore affect the activity and stability of proteins and signaling molecules within the matrix, and are vital for maintaining the integrity of cartilage and healthy connective tissue.
Proteoglycans are formed by joining protein cores to sugar chains called glycosaminoglycans (GAGs), which are composed of a repeating disaccharide unit. GAGs differ in the exact disaccharide units that make up their repeat sequence as well as their length, meaning that each GAG has different properties. However, all GAGs share the same structural pattern (see Figure 1).
Figure 1. Glycosaminoglycan RepeatingDisaccharide Units. The exact type of disaccharide units which make up a GAG may differ, as can the number of repeat disaccharide units, or length of the GAG. These variations confer different properties on each chain, although as can be seen from example GAGs (a), (b) and (c) above, each shares the same structural pattern.
a) 12121212121212121212121212121212
b) 3434343434343434343434343434343434
34343434343434343434
c) 1313131313131313131313131313131313
13131313131313
Chondroitin
Chondrotin is a GAG: one of the building blocks of proteoglycans and therefore extremely important for the maintenance of cartilage
Figure 2. A typical aggrecanase proteoglycan structure.
Among glycosaminoglycans, chondroitin is a particularly important component of connective tissue, cartilage and tendons. Composed of a chain of alternating units of the sugars N-acetyl-D-galactosamine and D-glucuronic acid, chondroitin molecules can have over 100 individual sugars, each of which may be sulfated in variable positions and quantities. This makes chondrotin a particularly versatile molecule.
Functions
The functions of a given chondroitin chain depend largely upon the properties of the particular proteoglycan to which it is attached. These functions may be broadly divided into structural and regulatory.
Structural
As a major component of the extracellular matrix, chondroitin plays a key role in maintaining the structural integrity of the extracellular environment. This function is typical of the large aggregating proteoglycans (aggrecan, versican, brevican and neurocan), which are collectively known as the lecticans.
As a component of the proteoglycan aggrecan, chondroitin is a major component of cartilage. The tightly packed and highly charged sulphate groups in the chondroitin generate electrostatic repulsion. The upshot of this is that any attempt to compress chondroitin is hindered by resistant repelling forces. This phenomenon invests cartilage with its resistance to compression, leading to its cushioning effects.
Figure 3. Proteoglycans Within the Extracellular Matrix. The chondroitin within proteoglycans generates electrostatic repulsion, which ultimately provides cartilage with its shock-absorbing properties and resistance to compression. As may be seen from the above below, the arrangement of many proteoglycans throughout the extracellular matrix helps to confer these widespread shock-absorbing effects: if ever pushed too close together, the negatively charged chondroitin molecules within the proteoglycans will repel each other.
One may liken the function of cartilage in this sense to that of a car or bike shock absorber. Loss of chondroitin from the cartilage therefore lessens cartilage’s cushioning effects, increasing the amount of grinding and shock experienced by bones at their joints. Typically, this deterioration will lead to arthritis over time.
Regulatory
Chondroitin readily interacts with proteins in the extracellular matrix because of its negative charges. These interactions are important for regulating a diverse array of cellular activities. The lecticans, for example, are a major part of the brain extracellular matrix, where chondroitin sugar chains function to stabilise the synapse (gap) areas across which neurons communicate.
How Chondroitin Helps Arthritis
The benefits of chondrotin in patients with arthritis are likely to be the result of a number of different effects, including anti-inflammatory activity, the stimulation of proteoglycan synthesis, and a decrease in the synthesis of proteoglycan-destroying enzymes. However, the most readily appreciable effect of chondroitin is straightforward in relation to its main functions.
As outlined above, one of the primary causative factors of arthritis is a decrease in proteoglycan (and therefore, chondroitin) levels, which leaves the cartilage more open to degradation. As the water and collagen within the cartilage deteriorates, the cartilage itself becomes less resilient, losing its cushioning, shock-absorbing properties and allowing bone to grind against bone. Chondroitin is one of the fundamental building blocks of proteoglycans – especially those most involved in the pathology of arthritis (eg. aggrecan). It plays a vital role in conferring cartilage with its cushioning and elastic properties. It helps to stabilise and regulate the extracellular matrix.
These beneficial properties can be lost as proteoglycan levels decrease with the progression of arthritis. Supplementing with chondroitin to help rejuvenate these properties therefore makes sense. As naturally-occurring chondroitin is depleted, it can be replaced by taking an oral supplement.
Not only is this measure simple, it’s effective. It has been proven to reduce patient reliance on pain-relieving drugs for arthritis and to increase their mobility in a multitude of clinical intervention trials. And it has an excellent safety profile. All in all, supplementing with chondroitin for the treatment of arthritis is a sensible choice.
- Access Economics Pty Limited (2001) ‘The Prevalence, Cost and Disease Burden of Arthritis in Australia,’ prepared for the Arthritis Foundation of Australia: Canberra, p.1.
- Tat SK, Pelletier JP, Vergés J, Lajeunesse D, Montell E, Fahmi H, Lavigne M, Martel-Pelletier J (2007) Chondroitin and glucosamine sulfate in combination decrease the pro-resorptive properties of human osteoarthritis subchondral bone osteoblasts: a basic science study, Arthritis Research and Therapy 9(6):R117; Monfort J, Martel-Pelletier J, Pelletier JP (2008) Chondroitin sulphate for symptomatic osteoarthritis: critical appraisal of metaanalyses, Current Medical Research and Opinion 2008 Apr 15 [Epub ahead of print].
