What Are the Key Structural Components of Articular Cartilage?
Articular cartilage protects the extremities of bones that unite to form moveable joints, such as the knees, hips, and shoulders. This super-smooth tissue functions as a cushion between the bones, allowing them to slide over each other painlessly and without friction. The key structural components that provide articular cartilage its distinct qualities are type II collagen and aggrecan. Type II collagen forms thick, rope-like fibrils that form a strong framework interwoven throughout the tissue. This collagen meshwork works as a net, providing cartilage strength and resilience to pulling and shearing forces during joint motions.
Aggrecan molecules can be found scattered throughout the collagen network. Aggrecan is a big, bottlebrush-shaped proteoglycan composed of several negatively charged sugar chains known as glycosaminoglycans. Aggrecan acts as a hydrophilic sponge because its sugar chains attract and absorb water. When the joint is compressed, the water-swollen aggrecan resists the loading, similar to a shock absorber. It presses back against the applied force, preventing the bones from grinding together. Aggrecan also draws water into the cartilage, keeping it wet and lubricated, allowing the bones to move past each other with ease.
How Does the Degradation of the Articular Cartilage Matrix Occur?
The cartilage matrix is mostly composed of collagen fibers and proteoglycans. MMPs (matrix metalloproteinases), which break down collagen, and ADAMTS(A Disintegrin and Metalloproteinase with Thrombospondin motifs), which cleaves aggrecan, are upregulated in osteoarthritis.
What Happens in the Enzymatic Breakdown of Collagen and Proteoglycans in Articular Cartilage?
Collagen and proteoglycans are the primary structural components that give cartilage its strength and shock-absorbing ability. Collagen forms stiff fibers that resist stretching, whereas proteoglycans behave as sponges to resist compression. The breakdown of these compounds weakens the cartilage. Specific enzymes can degrade collagen and proteoglycans. Collagen is broken down by enzymes known as collagenases. The primary collagenases present in cartilage are MMPs (matrix metalloproteinases) and cathepsins. MMP-1, MMP-8, and MMP-13 can cut collagen strands into pieces. Cathepsins K, L, S, and V have the ability to break down collagen.
Proteoglycans like aggrecan are broken down by enzymes named ADAMTS and cathepsins. ADAMTS-4 and ADAMTS-5 cut off pieces of aggrecan, allowing it to be released from the cartilage. Cathepsins can potentially degrade aggrecan further. MMPs also operate on other proteoglycans.
Usually, there is a balance between the enzymes that break down collagen and proteoglycans and proteins that inhibit these enzymes called TIMPs(Tissue inhibitors of metalloproteinases). However, in osteoarthritis, enzymes are more abundant than TIMPs. This imbalance eats away too much cartilage matrix. Inflammatory proteins known as cytokines also disrupt the balance by raising the levels of collagen and aggrecan-destroying enzymes.
How Does Mechanical Overloading Cause Articular Cartilage Degradation?
Mechanical overloading is defined as excessive or recurrent stresses on joints and cartilage caused by body weight and activities. As a weight-bearing tissue, articular cartilage is constantly subjected to mechanical stress. Physiological stresses are critical for keeping cartilage healthy and intact. However, excessive or repetitive overloading might harm the collagen meshwork and change chondrocyte metabolism to catabolism. Injurious mechanical conditions can cause fibrillation, fissures, and cartilage degradation over time. Cell death and matrix damage can result from direct overload or fatigue failure.
Overloading also activates stress-activated cation channels, which release calcium ions and activate degradative enzymes such as MMPs and ADAMTS. Cell-matrix interactions are disturbed, reducing chondrocytes' ability to detect and respond to mechanical stimuli. This can perpetuate matrix destruction through a positive feedback loop. Joint injury and obesity are common risk factors that increase contact stresses on cartilage and contribute to mechanical degradation. Managing weight and activity levels may help reduce damage from excessive joint loading.
How Does Inflammation Cause Articular Cartilage Degradation?
Inflammation of the synovial membrane (synovitis) is common in osteoarthritis and other joint ailments. Synoviocytes, chondrocytes, and invading immune cells release pro-inflammatory cytokines such as interleukin-1 and TNF-alpha during inflammation. These cytokines promote the development of proteolytic enzymes such as MMPs and ADAMTS enzymes, which break down cartilage matrix components. Additionally, they inhibit matrix synthesis by decreasing chondrocyte production of type II collagen and aggrecans.
Inflammation also causes the production of additional catabolic mediators such as prostaglandins, reactive oxygen species, nitric oxide, and neuropeptides within the joint area. Persistent synovitis can thereby shift cartilage homeostasis toward destruction rather than healing. Breakdown products of the cartilage matrix, such as collagen fragments and hyaluronan, can exacerbate inflammation, resulting in a self-perpetuating catabolic cascade.
What Are the Age-Related Changes That Weaken Cartilage?
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Glycation: Sugar molecules bond to collagen, making it stiff and brittle.
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Declining Cell Function: Cartilage cells become less responsive and make less matrix.
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Mitochondrial Dysfunction: In elderly cells, energy production is reduced.
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Oxidative Stress: Toxic free radicals accumulate which damages cells.
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Altered Enzymes: MMPs that break down collagen increase with age.
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Reduced Collagen Crosslinks: The number of connections between collagen fibers decreases.
The collagen network becomes rigid and frail, making it prone to mechanical cracks and tears with joint loading. Cartilage cells cannot properly maintain and repair the damaged matrix due to reduced function.
What Are the Subchondral Changes That Lead to Articular Cartilage Degradation?
Bone remodeling becomes unbalanced, resulting in bony spurs (osteophytes) on joint borders. Increased bone turnover and microcracks release inflammatory factors into the joint space. Stiffening of the subchondral bone increases mechanical stress on the cartilage above. Altered bone cell (osteoblast or osteoclast) activity interferes with bone-cartilage communication.
These subchondral bone alterations cause cartilage injury through:
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Inflammatory factors trigger cartilage-degrading enzymes.
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Abnormal joint mechanics overburden the cartilage.
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Disrupted bone-cartilage signaling that keeps joint homeostasis.
What Happens if There Is an Impaired Repair?
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With age and osteoarthritis, cartilage loses its ability to self-repair.
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Defect filling is diminished as cartilage cells proliferate and move less.
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Matrix synthesis slows, inhibiting intrinsic repair.
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Calcification and stiffness of cartilage also reduce natural repair capacity.
Factors contributing to poor repair include
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Altered cartilage cell metabolism and function.
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Changes in matrix composition.
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Pro-inflammatory joint environment.
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Reduced growth factor availability.
This age- and disease-related impairment of intrinsic repair allows cartilage defects to accumulate over time, resulting in progressive joint damage.
Conclusion
In conclusion, understanding the complex interplay of many elements that contribute to articular cartilage degradation is critical for developing effective prevention and management methods for disorders such as osteoarthritis. From the enzymatic degradation of critical structural components to mechanical stress and inflammation, each factor contributes significantly to cartilage integrity loss over time. Age-related alterations and reduced repair mechanisms make cartilage more vulnerable to injury. By addressing these issues completely, there is the potential to reduce joint degeneration and enhance overall joint health, hence improving the quality of life for people suffering from such disorders.
