Cartilage is a flexible connective tissue found in multiple areas of the body, including joints, the ear and nose, and intervertebral discs. Hyaline cartilage, the most abundant type of cartilage, plays a supportive role and assists in movement.
Formed by the process of chondrogenesis, the resulting chondrocytes are capable of producing large amounts of collagenous extracellular matrix and ground substance, which together form cartilage itself. This article will explain the structure, composition and formation of this structure.
Cartilage is a robust and viscoelastic connective tissue that can be found in joints between bones, the rib cage, intervertebral discs, the ear, and the nose. While more rigid and less flexible than muscle, cartilage is not as stiff as bone. These properties allow cartilage to serve as a support structure for holding tubes open or for proper locomotion. Examples of tubes include the cricoid cartilage and carina of the trachea, the torus tubarius at the opening of the auditory tube, and the auricle/pinna of the ear.
Chondrogenesis is the process by which cartilage is formed from condensed mesenchymal cells expressing collagen I, III and V. This process also involves differentiation of chondroprogenitor cells secreting molecules (aggrecan and type II, IX and XI collagen) that form the extracellular matrix. The chondroblasts that are caught in the matrix are called chondrocytes, and are the main type of specialized cells found in cartilage.
Chondrocytes are responsible for producing large quantities of collagenous extracellular matrix and ground substance that is rich in proteoglycans and elastin fibers. It is important to note for clinical purposes that the division of cells within cartilage is a very slow process, and cartilage growth consists of immature cartilage developing into a more mature state. Moreover, cartilage has a very slow turnover and is difficult to repair due to the fact that cartilage tissue is avascular (and also aneural). Its growth is not usually quantified by an increase in size or mass of the cartilage itself, but instead by its biomechanical properties.
Cartilage is classified as 3 types:
- elastic cartilage
- hyaline cartilage
Each type has varying amounts of elastin and collagen. Articular cartilage is specifically the smooth, white tissue covering the ends of bones where they come together to form joints. Healthy articular cartilage allows joints to move and glide over each other with very little friction, but is subject to damage and injury, as well as normal wear and tear.
The function of articular cartilage is dependent on the molecular composition of the extracellular matrix (ECM), which consists mainly of proteoglycans and collagen. As mentioned previously, the main proteoglycan in cartilage is aggrecan, which forms large aggregates with hyaluronan and are negatively charged to hold water in the tissue. The collagen (mainly type II), acts to constrain the proteoglycans and helps it hold its structure. Consequently, the ECM functions to respond to the tensile, shear, and compressive forces that are experienced by cartilage during mechanical use such as normal gait or weight-bearing movements.
Additionally, a glycoprotein known as lubricin that is abundant in the superficial layer of cartilage and synovial fluid plays a major role in bio-lubrication and wear protection of cartilage.
The layers of articular cartilage are defined by zones. Starting from the subchondral bone, there is a tidemark that is deep to the basal layer and separates true articular cartilage from the deeper cartilage, which is a remnant of cartilage anlage from longitudinal growth during childhood.
The deep, basal layer is found next, which consists of type II collagen that is perpendicular to the joint and crosses the tidemark. This basal layer also contains the highest concentration of proteoglycans, and round chondrocytes in this layer are arranged in columns.
The intermediate zone is adjacent to the basal layer, with an oblique or random organization of type II collagen. This zone is the thickest layer of round chondrocytes, with abundant proteoglycan content.
Finally, there is most superficial layer, also known as the tangential zone. This layer has type II collagen that is oriented in parallel to the joint. Instead of round chondrocytes, the superficial layer contains flattened chondrocytes, in addition to condensed collagen fibers and spare proteoglycans. This zone is also the only zone where articular cartilage progenitor cells have been identified.
Disadvantages of Cartilage
There are several diseases and processes that can affect cartilage. As mentioned before, the ECM is paramount in opposing shear, tensile, and compressive forces normally. Therefore, when this ECM is affected, it can lead to damage or injury. This can happen through physical mechanical forces, where excessive friction and applied forces wear down the cartilage (e.g. due to overuse or traumatic injury during athletics). Damage or injury can also happen through pathologic states, where ossification or breakdown of cartilage occurs due to dysfunction of cartilage-specific cells or synovial cells, or imbalances in the microenvironment surrounding the cartilage.
Cartilage has limited reparative capacities for a number of reasons:
- chondrocytes are bound in lacunae and cannot migrate to damaged areas
- cartilage does not have a blood supply so deposition of new ECM is very slow
- damaged hyaline cartilage is often replaced by fibrocartilage scar tissue with different biomechanical properties
Therefore, the standard treatments often involve total joint replacements (arthroplasty) or clever bioengineering techniques to regenerate articular cartilage through scaffolding and stem cell engineering.
While osteoarthritis is a disease that affects the whole joint, one of the most affected tissues is the articular cartilage, which is thinned or completely worn away. This results in “bone against bone” grinding within the joint that leads to reduced range of movement, loss of proprioception, and pain. Since osteoarthritis affects the joints exposed to the highest stress (knees, elbows, and hips), this condition is considered less of a disease and is rather regarded as a result of “wear and tear”. Treatment involves arthroplasty and chondroitin sulfate or glucosamine sulfate supplements.
Rheumatoid arthritis (RA) is a disease process where the body’s immune system attacks synovial cells, and therefore the lining of joint capsules, which is a tough membrane that encloses joints. RA frequently affects wrists, fingers, hips, knees, feet and ankles on both sides of the body (unlike osteoarthritis). It is a progressive and chronic autoimmune disease that triggers inflammation and results in damage to joint tissue, nearby bone and other organs, therefore indirectly affecting cartilage. RA progresses normally from various small to larger joints of the body, and damage to hands and feet is more likely to develop before damage to larger joints such as the hips or knees.
Treatment often involves various anti-inflammatory medications, such as non-steroidal anti-inflammatory drugs (NSAIDs) like aspirin or ibuprofen, or other COX inhibitors for symptomatic relief. More powerful immune system suppressing agents such as methotrexate and cyclosporine are sometimes used. Other medications aim to specifically inhibit inflammatory cytokines, such as tumor necrosis factor alpha, which helps drive inflammation in RA. Oftentimes, many of these medications are used in combination. Finally, treatment can also involve surgery or more progressive gene therapy drugs.
Achondroplasia is an autosomal dominant disease usually related to a mutation in the FGFR3 gene, which causes abnormal endochondral ossification to convert cartilage to bone, and results in dwarfism.
Costochondritis is a cause of chest pain resulting from inflammation of cartilage connecting the ribs to the sternum.
Tumors made up of cartilage tissue can also occur, but can be either benign or malignant in nature. While these tumors usually appear in bone, and rarely in pre-existing cartilage, they can invade cartilage. Benign tumors are called chondromas, and the malignant tumors are called chondrosarcomas.