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The extracellular matrix fills the spaces in between cells and collagen fibers in the musculoskeletal system, particularly in and around joints, tendons and ligaments. It serves multiple functions including protecting, nourishing and repairing the tissues within it. Glucosamine, which stimulates the synthesis of glucosaminoglycanes (GAGs) and collagen, and GAGs such as chondroitin sulfate and hyaluronic acid are useful for decreasing inflammation and damage with musculoskeletal injuries.
Glucosamine sulfate is one of the basic substrates for synthesis of these important macromolecules in connective tissue. The synthesis of glucosamine from glucose and glutamine is the rate-limiting step in GAG production, and hence in repairing cartilage. Following cartilage trauma or tearing, the body may not be able to make enough glucosamine for optimal healing. In addition, the ability to convert glucose to glucosamine declines with age because of a reduction in the amount of the enzyme glucosamine synthetase.
Taking glucosamine supplements can increase GAG levels significantly. Clinical trials have shown that glucosamine sulfate relieves the pain and inflammation of osteoarthritis. It also represents a safe alternative to nonsteroidal anti-inflammatory medications (NSAIDs - e.g., ibuprofen), which have been shown to inhibit repair and accelerate destruction of cartilage.
A recent review concluded that glucosamine is better tolerated than most other NSAIDs such as ibuprofen or piroxicam. And that in short-term clinical trials, glucosamine provided effective symptomatic relief for patients with osteoarthritis of the knee. In addition, glucosamine has shown promising results in modifying the progression of arthritis over a 3-year period. 
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Molecular Structure Of Common NSAIDs. Several studies have shown the beneficial effects of glucosamine on articular cartilage. A recent meta-analysis looking at all the available studies on glucosamine and chondroitin studies found that both, and especially glucosamine, were effective for the alleviation of pain, inflammation, and in maintaining and improving the structural integrity of joints. A recent study looking at the effects of both glucosamine and chondroitin on cartilage cells concluded that "by enhancing the "protective" metabolic response of chondrocytes to stress, glucosamine and chondroitin sulfate may improve its ability for repair and regeneration." In a more recent study, the authors found that glucosamine had preventative effects on arthritis in rats. A study published in 2002 done on athletic horses found that glucosamine inhibited cartilage catabolic responses and also prevented IL-1beta-induced increases in nitric oxide production, prostaglandin E2, and proteoglycan release.
A recent study showed that glucosamine was effective in improving function and decreasing pain in people who experienced knee pain likely as a result of prior cartilage injury and/or arthritis. In an earlier study, 68 athletes with cartilage damage in their knees were given 1500 mg of glucosamine sulfate daily for 40 days, then 750 mg for 90 to 100 days. Of the 68 athletes, 52 had a complete resolution of symptoms and resumed full athletic training. After four to five months, athletes were able to train at pre-injury rates. Follow-up exams 12 months later showed no signs of cartilage damage in any of the athletes.
At present, glucosamine is one of the recommendations now made by physicians for athletes and non-athletes alike in the management of injuries and arthritis. For example, in a recent article, physicians included the use of glucosamine in the medical management of early osteoarthritis of the knee in athletes. They have been used as a drug to treat osteoarthritis in Europe and are now gaining popularity in the U.S. Clinical trials both in the U.S. and abroad have confirmed their benefits and safety. The GAGs have been shown to repair and improve joint function as well as providing pain relief in chronic sufferers. Thus, glucosamine alone or in conjunction with chondroitin sulfate, and with other substances, is fast becoming the first treatment of choice for many joint and connective tissue pain sufferers.
Chondroitin sulfate is a major component of cartilage. It is a very large molecule, composed of repeated units of glucosamine sulfate. Like glucosamine, chondroitin sulfate attracts water into the cartilage matrix and stimulates the production of cartilage. Likewise, it has the ability to prevent enzymes from dissolving cartilage. Several studies have shown the beneficial effects of glucosamine and chondroitin sulfate on the musculoskeletal system (see above). A recent study found that the combination of chondroitin and glucosamine was more effective than chondroitin alone.
Although the absorption of chondroitin sulfate is lower than that of glucosamine (lower molecular units are better absorbed), a few recent studies have shown very good results from long-term treatment with chondroitin sulfate, reducing pain and increasing range of motion. For example, a one-year long, double-blind clinical study gave 800 mg of chondroitin sulfate to 42 patients of both sexes, aged 35-78 years with symptomatic knee osteoarthritis. The chondroitin sulfate was well tolerated and significantly reduced pain and increased joint mobility.
A recent review looked at the published reports with a view of determining the usefulness of chondroitin sulfate. The authors concluded that chondroitin sulfate plays a role in articular and bone metabolism by controlling cartilaginous matrix integrity and bone mineralization. There is some controversy about the absorption of chondroitin sulfate and thus its usefulness. Recent studies, however, have confirmed its absorption and oral bioavailability.
Some products naturally contain ultra high concentrations (min. 10%) of low molecular weight hyaluronic acid, which is vital for the health of soft connective tissue where it is a major component of the extracellular matrix, and is present in synovial joint fluid, cartilage, the eye, and in skin tissue both dermis and epidermis.
Hyaluronic acid (HA) is unique among the GAGs in that it does not contain any sulfate and is not found covalently attached to proteins as a proteoglycan. It is, however, a component of non-covalently formed complexes with proteoglycans in the ECM. Hyaluronic acid polymers are very large (with molecular weights of 100,000-10,000,000) and can displace a large volume of water. This property makes them excellent lubricators and shock absorbers. Hyaluronic acid may be able to slow down chondrocyte apoptosis (cartilage cell death) in OA by regulating the processes of cartilage matrix degradation.
Some products contain therapeutic amounts of glucosamine, chondroitin and HA, as separate ingredients. They may also contain several dozen other ingredients to help you prevent musculoskeletal problems and to deal with muscle aches, pains and injuries. These products are formulated to support muscle, cartilage and joint function in many ways. First of all, by maintaining tissue integrity it helps prevent musculoskeletal problems. Secondly, they may also provide the mechanisms and stimulus for repair of injured or damaged musculoskeletal tissue, whatever the cause. They also offer relief for aches and pains.
By providing several dozen ingredients that work along synergistic pathways to decrease inflammation and promote the body's natural synthesis and maintenance of joints, ligaments, muscles and tendons, these products help protect, prevent and help in the repair of musculoskeletal injuries and inflammation, regardless of the cause. These products are used by thousands of bodybuilders and other athletes, both amateur and professional, to help them get the most out of their training. It's also used by countless health professionals as an aid to both prevent and treat injuries. 
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The bones that form synovial joints are covered with cartilage. Tough fibrous tissue encloses the area between the bone ends and is called the joint capsule. The joint cavity within the capsule is lined with an inner membrane, called the synovial membrane.
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