A normal joint is designed to carry out a range of movements. Synovial joints have a dense fibrous capsule which may be reinforced by ligaments and muscles. The joint is lined by synovium and filled with synovial fluid for nutrition and lubrication of articular tissues. Articular cartilage is composed of connective tissue which is suited to distributing load and decreasing friction. Aspects of joints discussed here are: Cartilage, Articular Cartilage, Synovium Meniscus.

Cartilage

Cartilage is a form of connective tissue composed of chondrocytes and a specialised extracellular matrix. This matrix consists of water, collagen, proteoglycans and other components such as adhesives and lipids.

There are several different types of cartilage. Articular hyaline cartilage consists of a glassy and homogenous matrix with lacunae containing chondrocytes. Articular cartilage contains more collagen than other types of hyaline cartilage. It lines the bones of synovial joints and functions in load distribution and decreasing friction. The articular cartilage matrix is avascular, aneural and alymphatic relying on the process of diffusion to provide nutrients for the chondrocytes.

Other types of cartilage include fibrocartilage, elastic cartilage, and physeal cartilage. Fibrocartilage contains abundant thick bundles of mostly type I collagen which can be seen with the light microscope. This type of cartilage is found at ligament and tendon insertions into bone, in menisci, intervertebral discs, the symphysis pubis, temporomandibular and sternoclavicular joints. Fibrocartilage provides good resistance to shear and compression forces. Elastic cartilage is characterised by the presence of elastic fibres within the matrix which increase elasticity in tissues such as the external ear and trachea. Physeal cartilage provides longitudinal growth to immature long bones.

Articular Cartilage

Components

Chondrocytes (5% wet weight)

Chondroblasts which are derived from mesenchymal cells become trapped in lacunae and develop into chondrocytes. Chondrocytes are important in the control of matrix turnover through production of:

• collagen
• proteoglycans
• enzymes for cartilage metabolism.

Matrix

Water (60-80% wet weight)

• Articular cartilage is a highly hydrated material. Water distribution varies, making up 65% of wet weight at the deep zone and 80% at the surface.
• Weight bearing capacity is made possible through regional changes in water content which allow deformation of the cartilage surface in response to stress.
• Water provides nutrition and lubrication of cartilage.
• Increases in water content lead to:
• increased permeability
• decreased strength
• decreased Young’s modulus
• 
  
• Water content decreases with normal ageing.
• Water content increases in osteoarthritis

Collagen (10-20% wet weight) – (image 1)

• forms a cartilaginous framework which provides tensile strength.
• 90-95% is type II collagen with increased Gly, Lys-OH, Pro-OH and hydrogen bonding.
• small amounts of types V, VI, IX, X and XI collagen are present.

Proteoglycans (10-15% wet weight) – (image 2)

• half life of three months
• provide compressive strength
• regulate matrix hydration by providing a porous structure to trap and hold water
• composed of subunits of glycosaminoglycans (GAG’s - disaccharide polymers)
• • chondroitin-4-sulfate (decreases with age)
  • chondroitin-6-sulfate
  • keratin sulfate (increases with age)
• GAG’s are bound to a protein core by sugar bonds to form a proteoglycan aggrecan molecule.
• Aggrecan molecules are further stabilised by link proteins which bind them to hyaluronic acid to form a proteoglycan aggregate.

Adhesives

Molecular interactions between chondrocytes and collagen fibrils are mediated by fibronectin, chondronectin and anchorin CII.

Lipids are present in cartilage but their function is unknown.

Collagen molecules and proteoglycans interweave to form cartilage (image 3)

Layers (image 4)

Superficial Gliding Zone

• abundant tangentially oriented collagen fibres
• low proteoglycan concentration
• high water content
• discoid flattened cells, parallel to surface
• low metabolic activity (proteoglycan synthesis low)

Transitional Zone

• thicker fibrils
• oblique fibres
• cells arranged singly or in pairs
• high metabolic activity

Radial Zone

• increased collagen size
• vertical (radial) orientation of fibres
• high proteoglycan concentration

Tidemark

• Undulating barrier tangential to the surface which represents a plane of weakness.

Calcified Zone

• Hydroxyapatite crystals anchor the cartilage to the subchondral bone.

Metabolism

Collagen

Synthesis of collagen takes place in stages at various intracellular and extracellular sites. Post-translational modifications occur in the rER and Golgi.

Intracellular Events

• mRNA messages are translated into polypeptide chains which are released into the cisternae of the rER.
• The signal peptide is cleaved.
• Lysine and proline residues are hydroxylated.
• Hydroxylysine residues are glycosylated.
• N-linked sugars are added to the terminal portion of the polypeptide.
• Polypeptide chains form a triple helix molecule.
• Procollagen is formed through intrachain and interchain disulfide bonds which stabilise the polypeptides and determine the shape of the molecule.
• Procollagen is packed into secretory granules which move along microtubules to be released into the extracellular matrix

Extracellular Events

• Uncoiled terminal ends of procollagen are cleaved to form tropocollagen.
• Tropocollagen molecules aggregate and lysine and hydroxylysine residues are crosslinked to form a collagen fibril.
• Fibrils aggregate to form collagen fibres.

Collagen catabolism is poorly understood, but enzymatic processes and mechanical factors may be involved.

Proteoglycans

The process of proteoglycan synthesis begins with translation of mRNA to form a protein core to which glycosaminoglycan chains are added. The resultant aggrecan molecules are transported to secretory vesicles and released into the extracellular matrix. Link proteins and hyaluronate from the cell membrane bind to the molecules forming proteoglycan aggregates.

Proteoglycan catabolism depends on cleavage of globular domains resulting in non-aggregation of the resultant fragments.

Regulation of Growth

Cartilage synthesis is regulated by growth factors.

Platelet-Derived Growth Factors (PDGF)

• may have a role in healing cartilage lacerations

Transforming Growth Factor Beta (TGF-b )

• stimulates proteoglycan synthesis
• suppresses synthesis of type II collagen
• prevents the degradative action of plasmin and stremolysin through stimulation of formation of plasminogen activator inhibitor-1 and tissue inhibitor of metalloproteinase (TIMP).

Fibroblast Growth Factor (b-FGF)

• Stimulates DNA synthesis in articular chondrocytes in adult articular cartilage.
• may play a role in repair process.

Insulin-Like Growth Factor-I (IGF-I)

Changes With Ageing

With ageing cartilage becomes hypocellular and has decreased elasticity.

Chondrocytes

• increase in size
• increased lysosomal enzymes
• cartilage becomes hypocellular (cells stop reproducing)

Matrix

• Proteoglycans
• decrease in mass and size - decreased length of chondroitin sulfate chains
• change in proportion - increased keratin sulfate
• 
  
• Water content decreases
• Protein content increases

Healing of Articular Cartilage

Deep lacerations

• extend below the tidemark
• heal with fibrocartilage
• blunt trauma may cause osteoarthritic changes

Superficial lacerations

• above the tidemark
• chondrocytes proliferate but do not heal
• immobilisation leads to atrophy while continuous passive motion is beneficial to healing

Synovium

The interior surfaces of normal joints (except articular cartilage and menisci) are lined by a synovial membrane. Synovium is composed of vascularized connective tissue that lacks a basement membrane and contains two predominant cell types which reflect the function of the tissue.

Type A cells - important in phagocytosis

Type B cells - fibroblast-like cells which produce synovial fluid.

There are other undifferentiated cells that have a reparative role. Type C cells may exist as an intermediate cell type.

Synovial fluid produced by the synovium, is an ultrafiltrate of blood plasma containing in addition, hyaluronic acid, proteinase, collagenases and prostaglandins, but no red blood cells, clotting factors, or haemoglobin.

Function

• Nourishment of articular cartilage through diffusion.
• Lubrication of the joint space:

Joint lubrication can be divided into two types. It is likely that different types of lubrication become important in different types of movement.

Boundary lubrication (slippery surfaces) is where in response to a load, the joint surfaces are separated by a mono/multi molecular layer of low shear strength material (hyaluronate-protein complexes in the synovial fluid). This allows sliding motion while preventing adhesions or abrasions.

Fluid film lubrication is where fluid separates the joint surfaces. There are several different types.

Hydrodynamic Lubrication

• a wedge shaped film of fluid is pulled between two opposing surfaces
• a modification of this type is seen in human joints: elasto-hydrodynamic
• deformation of the surfaces also occur

Squeeze Film Lubrication

• Fluid forms a film after being forced from the articular surfaces subjected to a load.
• The viscosity of the fluid increases so that a gel is formed which has an osmotic pressure equivalent to the pressure applied.

Weeping (Hydrostatic) Lubrication

• A film is formed between the articular surfaces as fluid leaks out of the cartilage.

Boosted Lubrication (fluid entrapment)

Flow characteristics:

Flow is non-Newtonian (the viscosity coefficient m is not a constant; the fluid is not linearly viscous). Its viscosity increases as the shear rate increases.

Lubricin, a glycoprotein, is the key lubricating component of synovial fluid. Hyaluronan molecules in the knee become entangled and behave like an elastic solid during high strain activities (running, jumping).

Meniscus

The meniscus functions to deepen the articular surface of a number of synovial joints. By doing so it increases the contact area available for load distribution. These joints include:

• Acromioclavicular
• Sternoclavicular
• Glenohumeral
• Hip
• Knee

We will focus here on the meniscus of the knee joint.

Anatomy

The meniscus is a triangular, semilunar structure. Its peripheral border is attached to the joint capsule. In the knee, the medial meniscus is semicircular and the lateral meniscus is circular.

Components

The meniscus is composed of fibrocartilage.

Cellular components

These synthesise and maintain the extracellular matrix, and are responsible for anaerobic metabolism. Cells found are chondrocytes and fibroblasts, which are referred to as fibrochondrocytes.

Fusiform cells:

• in lacunae in superficial layer
• resemble chondrocytes and fibroblasts
• abundant ER and Golgi

Ovoid cells:

• surface and middle layer
• abundant ER and Golgi

Matrix components

Collagen

• primarily type I (55-65% dry weight), also types II, III, V, VI (5-10% dry weight)
• Superficial layer - mesh like fibres oriented radially
• Surface layer - (deep to superficial) collagen bundles aligned irregularly
• Middle layer - (deep) parallel to circumferential fibres

Elastin (0.6% dry weight)

Proteoglycans ® (1-3%

Glycoproteins ® dry weight)

Adhesive glycoproteins include fibronectin, thrombospondin.

Blood supply

The geniculate arteries supply the menisci. The outer 25% of the menisci are supplied by a circumferentially arranged plexus, and the remaining 75% receive supply via diffusion.

Tears that occur in the peripheral vascularised region (red zone) will heal via fibrovascular scar formation by fibrochondrocytes. Tears that occur in the central avascular regions (white zone), however, can't heal.

Nerve supply

The outer two-thirds of the menisci is innervated by type I and type II nerve endings which are concentrated in the anterior and posterior horns, with few fibres in the meniscal body.

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