Cartilage tissue is a type of connective tissue that literally forms the biological glue and twine that holds your body together. Cartilage forms the cushions that keep your bones from grinding against each other. Even your nose is made largely of cartilage. Cartilage is found in almost all joints including the knee, hip, elbows, and shoulders.

You can visualize connective tissue as somewhat similar to Jell-O, but more dense. Our organs and bones are held together by special cells, fibers and ground substance, together called connective tissue. Skin is mostly connective tissue. If you stretch your imagination and think of your body as a bowl of Jell-O containing various fruit pieces such as grapes, pears, peaches, and bananas, then the Jell-O would be connective tissue while the fruit pieces would be organs. Connective tissues hold everything in place. Connective tissue can be condensed and made harder in a variety of ways leading to ligaments, tendons, cartilage, and even the cornea of the eye.

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What is connective tissue made of?

There are three major components to connective tissue.

1) Cells that are responsible for forming fibers and proteoglycans. Three major types of cells include fibroblasts (mostly in skin), chondrocytes (mostly in cartilage), and osteoblasts (mostly in bone). Once the fibers and proteoglycans are made in chondrocytes, they are taken outside of the cells to form part of the ground substance. The ground substance is also called the matrix.

2) Fibers include collagen, reticulin and elastin.

3) Proteoglycans are abundant, large, molecules of a variety of shapes and sizes and compositions. As with the fibers, they are also made by cells and then taken outside of the cells to form part of the gelatinous ground substance. See Diagram 3. The proteoglycans interact with the fibers, such as collagen, to help maintain the health and resiliency of connective tissue. The amount of proteoglycans within cartilage decreases with age, thus contributing to the development of arthritis.
     Proteoglycans are complex molecules made up of a protein core with many long-chained sugar molecules linked to it. Glucosamine or galactosamine sugars are attached to another sugar, such as glucuronic acid, to form a double sugar combination called a disaccharide. Repeating disaccharide units make glycosaminoglycans (formerly called mucopolysaccharides). When many of these glycosaminoglycans units are attached to a protein core, we call the whole combination a proteoglycan. Cartilage, then, is made of countless of these proteoglycans in close proximity to fibers, such as collagen, and cells called chondrocytes. The whole proteoglycan unit resembles a toothbrush with bristles coming out from all sides, the handle being the long protein core and the bristles being the glycosaminoglycans. Some of the proteoglycans possess up to 100 glycosaminoglycan chains. There are at least six types of glycosaminoglycans including hyaluronate, chondroitin, dermatan, keratan, heparin, and heparan. Hyaluronates are the most abundant. Interestingly, the dominant sugar within hyaluronate, heparin and keratan is glucosamine, specifically N-acetyl-glucosamine. The most common sugar within chondroitin and dermatan is galactosamine, a sugar similar to glucosamine. It is a biochemical fact that glucosamine can be converted to galactosamine.

What makes cartilage absorb shock?

The long glycosaminoglycan chains are negatively charged and thus repel each other. When two molecules have the same electrical charge, they repel each other and if they have opposite charges, they attract. This characteristic of repelling allows proteoglycans to occupy a lot of space in connective tissue and cartilage. It also gives them the ability to be resilient, permitting compression and re-expansion. Thus they are ideally suited to be part of cartilage (such as knee cartilage) which is exposed to a lot of stress and weight. Cartilage can thus withstand the compressive load of weight bearing and then re-expand to its previous dimensions when that load is relieved. Proteoglycan synthesis is influenced by glucosamine supplementation and a variety of physical (exercise), biochemical (calcium levels, vitamins, hormone levels, and medicines) and mechanical effects.

What is cartilage made of?

Cartilage is a form of connective tissue but denser. It also contains cells (chondrocytes), fibers and a lot of proteoglycans. Chondrocytes are the cells that are responsible for the making and maintenance of the ground substance (matrix) in cartilage, and they do so under difficult conditions of lacking a direct blood supply, and under low oxygen levels. The number of chondrocytes in cartilage tissue decreases with age.
   The composition of adult articular cartilage consists mostly of water (about 70-80%), along with collagen fibrils (about 10-15%), proteoglycans (about 5 to 10%), and various other proteins. Of the three most prevalent components of human cartilage (water, proteoglycans and collagen) it appears that proteoglycans are the most affected by nutritional supplements.

Where is cartilage found?

Cartilage is a padding that lines the ends of bones that form joints. For instance, the bottom tip of the femur (thighbone) has cartilage that forms a joint with the top part of the tibial bone in the leg, which also is made of cartilage, thus forming the knee joint. Thus, every time you take a step, the cartilage absorbs the pressure exerted on the knee joint. The parts of cartilage that have the ability to absorb this pressure are the fibers and proteoglycans.
   The many biochemical and metabolic abnormalities that can occur in cartilage tissue with osteoarthritis, may well explain why numerous nutritional approaches need to be addressed. Although glucosamine is an important nutrient, we shouldn’t think that it could solve all the problems of a complex tissue, as is cartilage. Proper cartilage nutrition would consist of a cocktail of numerous nutrients that, when combined, create synergistic healing.

How are nutrients supplied to cartilage?

Normal adult cartilage tissue does not contain any nerves or blood supply. This is an important distinction to be made compared to other human tissues. The source of nutrients for cartilage comes from synovial fluid (see Diagram 2) that bathes the surrounding joint. This fluid consists of some filtrates of blood plasma, proteoglycans and proteins from specific synovial cells. Synovial fluid has two important functions. First, it serves to lubricate cartilage as they slide over each other during movement. Second, it supplies the nutrients, and removes the waste products from the cells within cartilage. These cells, called chondrocytes, have no direct blood supply. Because cartilage tissue exchanges nutrients and waste by-products by passive diffusion, joint movement (i.e. physical activity) is essential for the maintenance of normal articular cartilage. Smoking interferes with joint injury repair since cigarette toxins interfere with cartilage cell growth.

What happens to cartilage with age?

As we get older, we lose some of these proteoglycans and thus starts the process of arthritis. Cartilage deteriorates, becomes thinner and more easily damaged. The shock-absorbing abilities are diminished. The result is aches and pains in joints and surrounding tissues.
     The problem in OA is that there is not only deterioration to the cartilage, but reaction to the damage. The breakdown of cartilage, mostly due to loss of proteoglycans, leads to development of erosions where the surface becomes uneven and pitted. There are several enzymes known to destroy the cartilage matrix including hyaluronidase, collagenase, and phospholipase A2. They are part of the normal process of cartilage destruction and making and repair of new ones. Cartilage thins when the process of repair cannot keep up with the destruction.

Knee cartilage
The clinical consequences of articular cartilage defects of the knee, such as torn knee cartilage, are pain, swelling, mechanical symptoms, athletic and functional disability, and osteoarthritis. Full thickness articular cartilage defects have a poor capacity to heal. Meniscal injuries are the most common surgically treated knee injury in the United States.
   Anterior cruciate ligament injuries are common among athletes. Anterior cruciate ligament injuries are functionally disabling; they predispose the knee to subsequent injuries and the early onset of osteoarthritis.

Articular cartilage and Mechanical Destruction
Articular cartilage is a complex tissue with a limited endogenous repair capacity. Mechanical injury is considered to be a major cause of articular cartilage destruction and therefore a risk factor for the development of secondary osteoarthritis. Mechanical injury induces damage to the tissue matrix directly or mediated by chondrocytes via expression of matrix-degrading enzymes and reduction of biosynthetic activity. As a consequence the mechanical properties of cartilage change. Mechanical injury induces tissue swelling and decrease in both the compressive and shear stiffness of articular cartilage, probably due to disruption of the collagen network. Injurious compression induces chondrocyte death by necrosis and apoptosis and the remaining cells decrease their biosynthetic activity. The tissue content of proteoglycans also decreases with time in injured cartilage, and the tissue loses its ability to respond to physiological levels of mechanical stimulation with an increase in biosynthesis. Immature cartilage seems to be more vulnerable to injurious compression than more mature tissue.

Knee cartilage teat
Damage to the meniscus, a shock-absorbing cartilage in the knee, is a common finding on MRIs in middle-aged and elderly persons and, in most cases, it causes no symptoms. The New England Journal of Medicine, September 11, 2008.

Glossary
Amino acid-one of the building blocks of protein. There are twenty amino acids in our bodies that become part of protein.
Cartilage - a type of dense connective tissue present at the end of bones that help form joints. Cartilage is also found in the larynx, air passages, nose, and ear.
Chondrocyte - a cell in cartilage tissue that helps form chondroitin and other substances that provide the cushion and resiliency of cartilage tissue.
Chondroitin - a nutrient made of two amino-sugar molecules attached to each other that helps form cartilage tissue.
Disaccharide - two sugar molecules joined to each other. Examples include lactose, sucrose, chondroitin, and others.
Double blind - a research study where neither the researchers nor the volunteers know who's getting the medicine and who's getting the placebo until the code is broken at the end of the study.
Glucosamine - a nutrient made from sugar and nitrogen that helps form cartilage tissue. Glucosamine is commercially produced from chitin, the shell of shellfish.
Glycosaminoglycans (GAGs) - long chains of chondroitin molecules attached to each other. GAGS are attached to a protein molecule to form proteoglycans.
NSAIDs, non-steroidal anti-inflammatory drugs - these are medicines, such as aspirin, ibuprofen, naprosyn, and others that reduce inflammation. Side effects with frequent high dose use can include stomach upset with ulcers, along with kidney damage and hearing loss.
Placebo controlled - a study where a group of volunteers gets a medicine and another group, called the control, gets a placebo.
Proteoglycans - large compounds made from chains of chondroitin that are attached to a protein molecule. Proteoglycans help cartilage tissue be resilient to pressure and weight bearing.

Composition of Articular Cartilage
Articular cartilage consists of a sparsely distributed population of highly specialized cells called chondrocytes that are embedded within a matrix and provide articular cartilage with remarkable mechanical properties. Chondrocytes form the tissue matrix macromolecular framework from three classes of molecules: collagens, proteoglycans, and noncollagenous proteins.
   Throughout life, articular cartilage undergoes internal remodeling as the cells replace matrix macromolecules lost through degradation. Aging decreases the ability of chondrocytes to maintain and restore articular cartilage and thereby increases the risk of degeneration of the articular cartilage surface. Progressive degeneration of articular cartilage leads to joint pain and dysfunction that is clinically identified as osteoarthritis.

Cartilage ear piercing
Body piercing at sites other than the earlobe has grown in popularity. The tongue, lips, nose, eyebrows, nipples, navel, and genitals may be pierced. Complications of body piercing include local and systemic infections, poor cosmetic outcome, and foreign body rejection. Swelling and tooth fracture are common problems after tongue piercing. Minor infections, allergic contact dermatitis, keloid formation, and traumatic tearing may occur after piercing of the earlobe. "High" ear piercing through the ear cartilage is associated with more serious infections and disfigurement.

Cartilage Questions
Q. I have recently been experiencing clicking (crepitus) and pain in my left knee and pain, especially when I descend a flight of stairs. I read Dr. Theodosakis' book, The Arthritis Cure (revised edition) and noted with great concern that on p. 43, he indicated that NO is involved in early cartilage cell death, which glucosamine can counteract. Since I take 2,000 mg of l-arginine t.i.d. to regulate blood pressure, improve memory, enhance sexual performance, I am worried that I am harming myself instead of helping myself with respect to l-arginine supplementation. I am also taking 500 mg of glucosamine t.i.d. and 400 mg of chondroitin t.i.d. for the knee. Your website discusses l-arginine for several of the same reasons that I am taking it, and I would like to know if you are aware of the relationship between NO and its effect on cartilage. Also, do you have any comment on Dr. Theosodakis' recommendation that people with osteoarthritis dose themselves with avocado soybean unsaponfiables (ASU), as he discusses in his book?
   A. We have not come across any studies that mention arginine use leading to cartilage damage. Also, we have not seen any studies of any length that say avocado soybean oil should be used by those with arthritis.

Q. A number of supplement suppliers are emphasizing the superiority of chondroitin from shark cartilage versus bovine sources due to the risk of mad cow disease. Do you have any preference yourself?
   A. To the best of my knowledge, there does not seem to be a risk for mad cow disease regarding the use of chondroitin from bovine cartilage. Since there have not been any studies comparing bovine cartilage chondroitin versus chondroitin from shark cartilage, it is not possible to say with certainty which source is better.

Q. I'd like to know if Dr. Sahelian knows of any particular foods or nutrients or supplements that are effective in aiding healing and repair/rebuilding of ligaments and tendons. I ask this as a Physical Therapist (intern) who's particularly interested in Sports medicine and sports injuries. I'm aware of glucosamine and chondroitn and MSM for healing of cartilage in joint structures, but are there nutrients that enhance healing of tendons and ligaments? Would glucosamine, chondroitin and MSM also play a role in healing of these structures?