Basic Sciences 2023, Jan, 25 | 12:00 am

Cartilage and Joint

Cartilage and Joint

  • Hyaline cartilage characteristics

    • Articular bearing surface

       

       

       

      FIG. 1.25 Pathologic features of avascular necrosis. Illustration of articular cartilage (A), necrotic bone (B), reactive fibrous tissue (C), hypertrophic bone (D), and normal trabeculae (E).

      From Steinberg ME: The hip and its disorders, Philadelphia, 1991, Saunders, p 630.

       

    • Decreases friction and distributes loads

      • Coefficient of friction in healthy human joint is less than that of ice on ice (0.002–0.04).

    • Shock-absorbing cushion resists shear/compression.

      • Withstands impact loads up to 25 N/mm2

    • Avascular, aneural, and alymphatic

      • Receives nutrients and oxygen from synovial fluid via diffusion

      • Heals poorly

    • Anisotropic: Properties vary with direction of force

    • Viscoelastic: Properties vary according to rate of force application.

    • Biphasic—property of liquid and solid

    • Cartilage homeostasis disrupted by:

      • Direct trauma/excess or inadequate forces

      • Loss of underlying bone structure

      • Genetic defects in normal structure/function

      • Chemical/enzymatic threats

  • Hyaline cartilage composition

    • Water

      • Approximately 75% of cartilage

      • Highest at surface or superficial layers

      • Recurrent low-level forces shifts water in and out of extracellular matrix (ECM)

      • Responsible for nutrition and lubrication

      • H2O decreases with aging

      • H2O increases in osteoarthritis (Fig. 1.26)

    • Collagen

      • Makes up approximately 15% of wet weight (60% of dry weight) (Fig. 1.27; Table 1.19)

      • Type II collagen: 90%–95% of collagen

        • Triple helix of α chains (derived from COL2A1

          gene)

        • Genetic defects of type II cause achondrogenesis (lethal at birth), spondyloepiphyseal dysplasia congenita, precocious arthritis

      • Types IX and XI are “linking collagens”

      • Type X found only near calcified cartilage, including:

        • Calcified zone of articular cartilage’s tidemark

        • Hypertrophic zone of the physis (genetic defect of type X leads to Schmid metaphyseal chondrodysplasia)

        • Fracture callus and calcifying cartilaginous tumors

      • Provides shear and tensile strength

Table 1.18

Common Types of Osteochondrosis

 

 

Disorder Site Age (YR)

Van Neck disease

Ischiopubic synchondrosis

4–11

Legg-Calvé-Perthes disease

Femoral head

4–8

Osgood-Schlatter disease

Tibial tuberosity

11–15

Sinding-Larsen-Johansson syndrome

Inferior patella

10–14

Blount disease in infants

Proximal tibial epiphysis

1–3

Blount disease in adolescents

Proximal tibial epiphysis

8–15

Sever disease

Calcaneus

9–11

Köhler disease

Tarsal navicular

3–7

Freiberg infarction

Metatarsal head

13–18

Scheuermann disease

Discovertebral junction

13–17

Panner disease

Capitellum of humerus

5–10

Thiemann disease

Phalanges of hand

11–19

Kienböck disease

Carpal lunate

20–40

 

 

 

 

 

 

FIG. 1.26 Articular cartilage changes in osteoarthritis and aging. Arrows indicate an increase (when pointing up) or a decrease (when pointing down).

From Brinker MR, Miller MD: Fundamentals of orthopaedics, Philadelphia, 1999, Saunders, p 9.

 

 

FIG. 1.27 Macrostructure to microstructure of collagen. Although the majority of the collagen in bone, tendon, and ligament is type I, most of the collagen in cartilage is type II. Collagen is composed of microfibrils that are quarter-staggered arrangements of tropocollagen. Note the hole and pore regions for mineral deposition (for calcification). Vitamin C (ascorbic acid) is an enzymatic cofactor needed to form the hydroxylated version of the amino acids proline and lysine, which allow the twists to form the triple helix from the polypeptide α chains. EM, Electron microscopy.

Modified from Brinker MR, Miller MD: Fundamentals of orthopaedics, Philadelphia,

1999, Saunders.

 

Table 1.19

 

Collagen Types, Locations, and Related Genetic Disorders a‌

 

 

Type Location Genetic Disease

I

Bone, tendon, meniscus

Osteogenesis imperfecta

Disc annulus, eye (sclera), skin

Ehlers-Danlos syndrome

II

Articular cartilage

Disc nucleus pulposus, eye (vitreous humor)

Achondrogenesis (lethal) Hypochondrogenesis Spondyloepiphyseal

dysplasia congenita

Kniest dysplasia Stickler syndrome Precocious arthritis

III

Skin, blood vessels

Ehlers-Danlos syndrome

IV

Basement membrane: kidney, ear, eye (basal lamina)

Alport syndrome

V

Articular cartilage (in small amounts)

Ehlers-Danlos syndrome

VI

Articular cartilage (in small amounts); tethers chondrocyte to pericellular matrix

Bethlem myopathy

Ullrich congenital muscular dystrophy

VII

Basement membrane (epithelial)

Epidermolysis bullosa

VIII

Basement membrane (epithelial)

Corneal endothelial dystrophy

IX

Articular cartilage (in small amounts)

Multiple epiphyseal dysplasia

(one type)

X

Hypertrophic zone or tidemark of cartilage (associated with calcified cartilage)

Metaphyseal chondroplasia, Schmid type

XI

Articular cartilage (in small amounts); acts as an adhesive

Otospondylomegaepiphyseal dysplasia

XII

Tendon

 

XIII

Endothelial cells

 

a More common orthopaedic diseases are in bold.

  • Contributes to viscoelastic behavior in that it restrains “swelling” of aggrecan

  • Proteoglycans

    • Make up approximately 10% of wet weight (30% of dry weight) (Fig. 1.28).

    • Half-life of 3 months

    • Provide compression strength

    • Responsible for cartilage’s porous structure

    • Trap and hold water

    • Produced by chondrocytes

    • Most common is aggrecan.

      • Large macromolecules shaped like bristle brushes (see Fig. 1.28)

      • Composed of repeating disaccharide subunits or glycosaminoglycans attached to protein core

        • Repeating carboxyl and sulfate groups which are ionized in solution to COO − and SO3 −

        • Repel each other but attract positive

          cations

        • Increase osmotic pressure, which traps and holds water and is responsible for ECM’s hydrophilic behavior

        • Provides turgor of matrix

        • Chondroitin sulfate (most prevalent glycosaminoglycan in cartilage)

          • Chondroitin 4-sulfate decreases with age

          • Chondroitin 6-sulfate remains constant

        • Keratin sulfate

          • Increases with age.

      • Multiple core proteins in turn attached to hyaluronic acid (through link proteins) producing proteoglycan aggregate

  • Chondrocytes

    • 1%–5% of wet weight

    • Only cells in cartilage

      • Derived from undifferentiated mesenchymal precursors

      • BMP-2 and the transcriptional factor SOX-9 important in regulating chondrocyte differentiation and formation

    • Mechanotransduction—metabolism modulated via mechanical stimulation

      • Cyclical loads of walking stimulate chondrocytes to form matrix

      • Low loads (1–5 MPa) at moderate frequency (≈1 Hz)

      • Primary cilia are the mechanosensory organ “antennae” for cells.

    • Produce the extracellular matrix of collagen and proteoglycans

      • Intracellular synthesis of procollagen, link peptide, hyaluronic acid, proteoglycans

      • Extracellular assembly of component parts

    • Produce proteins and enzymes and maintain matrix

      • IL-1β (also from synovium and WBCs): main cartilage destroyer

      • Metalloproteinases—break down cartilage matrix

        • Collagenase—dissolves collagen (matrix metalloproteinase 13 [MMP-

          13])

        • Aggrecanase—degrades proteoglycans (extracellular protease enzyme ADAMT)

      • Enzyme inhibitors—protect cartilage

        • Tissue inhibitors of metalloproteinases (TIMPs)

        • Plasminogen activator inhibitor-1 (PAI-1)

    • Chondrocytes are most dense and most active in the superficial zone.

    • Deeper cartilage zone chondrocytes less metabolically active

      • Decreased rough endoplasmic reticulum

      • Increased intraplasmic filaments (degenerative products)

  • Other matrix components

    • Nonaggregating proteoglycans

       

       

      FIG. 1.28 Proteoglycan aggregate and bristle brush–shaped aggrecan molecule. Sulfate ions are transmitted by DTDST protein; a defect in the DTSDT gene causes diastrophic dysplasia (short stature with hitchhiker’s thumbs and cauliflower ears).

      Modified from Brinker MR, Miller MD: Fundamentals of orthopaedics, Philadelphia, 1999, Saunders, p 9.

       

      • Also known as small leucine-rich proteoglycans (SLRP)

      • Important in matrix assembly and cell signaling

      • Decorin and fibromodulin bind to type I and type II collagens and organize and stabilize framework

    • Other matrix proteins

      • Fibronectin—binds to integrins (transmembrane receptors)

        • Increased in osteoarthritis

      • Chondronectin—mediates attachment of chondrocytes to type II collagen

      • Anchorin CII—binds chondrocytes to type II collagen

  • Articular cartilage layers ( Fig. 1.29)

    • Zone 1: superficial or tangential zone (10%–20% of thickness)

      • Thin lamina splendens

      • Flat chondrocytes

      • Collagen fibers

        • Highest concentration

        • Parallel to joint surface strength against shear

        • Greatest tensile stiffness

      • Lowest concentration of proteoglycans

      • Highest concentration of water

    • Zone 2: middle or transition zone (40%–60% of thickness)

      • Collagen fibers more random and less dense

      • High levels of water and proteoglycan

    • Zone 3: deep zone (30% of thickness)

      • Lower water content

      • Highest concentration of proteoglycan

      • Chondrocytes and collagen fibers arranged perpendicular to articular surface

    • Zone 4: calcified cartilage zone

      • Begins at tidemark

      • Transitions stiffness from flexible cartilage to rigid subchondral bone

      • Low concentration of proteoglycans

      • Type X collagen found here

      •  

         

        FIG. 1.29 The layers of articular cartilage and their characteristics and functions. C,

        Cytoplasm; EM, electron micrograph; IF, intermediate filaments; N, nucleus. Composite from Mark R. Brinker MR, Daniel P, O’Connor DP: Basic science. In Miller MD et al, editors: Miller orthopaedic review, Philadelphia, 2012, Saunders, Fig. 1.40; Buckwalter JA, Mankin HJ: Articular cartilage. Part I: tissue design and chondrocyte-matrix interactions, J Bone Joint Surg Am 79:600–6