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Introduction
  Joint Pain       Cartilage      
 
 
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About Cartilage

Types of cartilage

  • Hyaline cartilage covers the ends of bones within joints to allow smooth movement (also known as articular cartilage). It is also found in the growth plates of long bones in children.
  • Fibrocartilage is found in the intervertebral disc, jaw (TMJ) joint, meniscus of the knee joint, and at the site of fracture healing.
  • Elastic cartilage is found in the epiglottis (valve preventing food entering the airway) and eustachian tube (connecting the throat to the middle ear).

Hyaline Cartilage

  • Hyaline (articular) cartilage has a complex structure whose biochemical makeup varies between different joints. It does not have it's own blood supply and is insensitive to pain due to the lack of nerve fibres.
  • The predominant collagen in articular cartilage is type II, while the predominant collagen in meniscus of the knee is type I.
  • Cartilage constantly undergoes dynamic remodelling, being eroded by matrix metalloproteinases (MMP's), and being reformed by chondrocyte activity (cartilage forming cells).
  • It is being continuously bathed in synovial fluid which is produced by synovial membrane at the margin of the joint surface.
  • Nutrients pass from the underlying periosteum (superficial bony layer) through the cartilage matrix by diffusion, to reach the chondrocytes. Nutrients also reach the surface of cartilage from the synovial fluid (lubricating fluid) which circulates around the joint space.
  • Hyaline cartilage has the following typical composition:-
    • 70% water
    • 15% collagen
    • 15% proteoglycans (protein-glycosamine molecules), chondrocytes (cartilage producing cells), non-collagen proteins, lipids and inorganic material.
  • The chondrocytes sit within a matrix of proteoglycans and collagen which are related in such a way as to give the cartilage its important compressive and tensile properties.
  • The collagen/proteoglycan matrix provides the structural framework of the tissue and also forms a fluid compartment for transport of nutrient, waste products, chemical messengers and hormones, to and from the chondrocytes.
  • Hyaline cartilage is divided up in to 4 different zones each containing different collagen organisation as well as different amounts of proteoglycans:-
    1. Superficial tangential zone (10-20% of the cartilage thickness).
    2. Middle zone (60% of the cartilage thickness).
    3. Deep zone (30% of the cartilage thickness).
    4. Calcified cartilage zone where the cartilage interfaces with the bone.
  • The superficial or tangential zone contains the highest collagen content, about 85% by dry weight. In addition, the collagen fibrils are oriented parallel to the joint surface, indicating that the purpose of this zone may be primarily to resist shear stresses. The amount of collagen decreases in each zone moving closer to the tidemark (see diagram), dropping to 68% in the middle zone.
  • If cartilage becomes too water-logged it swells and loses it's resilience to injury due to a change in it's mechanical behaviour. Factors controlling the water content are:-
    • Concentration of proteoglycans - proteoglycans within the collagen matrix have a strong negative electrical charge, which helps repel water molecules.
    • Organization of the collagen network
    • Stiffness and strength of the collagen network - determined by the compaction of proteoglycans in the matrix.
  • In OA degradation of the collagen matrix causes an increase in the cartilage water content, altering its mechanical properties and reducing its ability to with stand injury.

About Synovial Fluid

Functions

  • Lubricate joint surfaces (Hyaluronic Acid and water).
  • Nourish chondrocytes.
  • Remove waste and debris from joint.
  • Medium for white blood cells to circulate and phagocytize debris.
  • Hyaluronic Acid and protein account for the higher viscosity.

Composition

  • Produced as a dialysate of plasma.
  • White Blood Cells = < 200/mm3.
  • Monocytes and macrophages 40-50%.
  • Lymphocytes 40-50%.
  • Neutrophils < 8%.
  • Glucose content same as plasma.
  • Red Blood Cells < 100/mm3.
  • Hyaluronic acid - enhances viscosity.
  • Protein < 2 g/dl.
  • Ionic content same as plasma.

About Osteoarthritis

Osteoarthritis Risk Factors

Risk Factors
Hip
Knee
Hand
Gender
M > F
F > M
F > M
Increasing Age
++
++
++
Obesity
+
++
+/-
Family History
+/-
+/-
++
Joint Shape
++
+
-
Joint Trauma
+
++
+/-
++ greatly increases risk, + increases risk, +/- possibly increases risk, - no increased risk

Current Theories of Osteoarthritis (OA)

  • In OA the balance between cartilage degradation and reformation is upset, with a net loss of collagen and proteoglycans from the matrix. This is in contrast to rheumatoid arthritis where there is inflammation of the synovial lining, associated with progressive joint destruction.
  • The initial response is a proliferation of chondrocytes, which produce an increased amount of matrix containing collagen and proteoglycans.
  • As the disease progresses, the ability of chondrocytes to respond is outstripped by progressive cartilage degradation.
  • Fibrillation, erosion and cracking initially appear in the superficial layer of cartilage and progress over time to deeper layers, resulting eventually in large clinically observable erosions.
  • There are distinct differences in the observed changes in cartilage between old age and OA. OA cartilage has a greater content of denatured collagen, a different chondroitin content, and a greater matrix metalloproteinase (MMP) activity causing increased cartilage degradation.
  • Arthritis pain research has shown that Interleukin-1 (IL-1), a pro-inflammatory molecule, is an important molecule in OA. It has the following actions:-
    • Induces chondrocytes to produce more cartilage matrix.
    • Stimulates the synovial cells to produce more metalloproteinases, the enzymes involved in denaturing cartilage.
    • Inhibits the synthesis of type II articular cartilage.
    • Inhibits the synthesis of proteoglycans by chondrocytes.
  • Therefore IL-1 not only causes degradation of cartilage, but suppresses any attempt to repair it.
  • Cartilage repair is dependant on the production of matrix by chondrocytes. Chondrocyte activity can be stimulated by locally produced growth factors like Transforming Growth Factor B (TGF-B) and Basic Fibroblastic Growth Factor (B-FGF) These molecules can counteract the cartilage degradation caused by high IL-1 levels. TGF-B also switches off the production of IL-1.
  • In advanced OA however, cartilage degradation associated with high IL-1 levels far outstrips any attempts at repair by these growth factors.
  • Future targets for treating OA include reducing metalloproteinase (MMP) activity, and inducing collagen matrix synthesis.
  • There is weak evidence to suggest that supplementing your diet with Glucosamine, Chondroitin and MSM can produce mild to moderate arthritis pain relief by improving cartilage function, leading to healthy joints.
  • Joint health can also be improved by increasing the levels of hyaluronic acid within the synovial fluid - see Hyaluronic Acid for more information.
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