bone & cart lecture

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    CARTILAGE

    &

    BONE

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    CARTILAGE & BONE

    Skeletal system supporting / connective tissue

    Functional differences relate to diff. nature &

    proportion of ground substance & extracellular

    matrix

    BONE: rigid protective support / framework

    CARTILAGE :semi-rigid (limited)

    :precursor of bone

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    CARTILAGE

    FUNCTIONS:

    - Bears mechanical stress

    - Support soft tissues- Shock absorber & sliding area for joints

    - For development & growth of long

    bones

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    CARTILAGE

    Chondrocytes

    (lacunae)

    - synthesize &

    secrete theextracellular

    matrix

    - active

    Extracellular

    matrix

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    CARTILAGE EXTRACELLULAR MATRIX

    1. Proteoglycans - sulfated GAG (chondroitin

    sulfate & keratin sulfate) predominate w/

    hyaluronic acid, forming central backbone of thecomplex

    2. Collagen & elastic fibers electrostatic bonds b/w

    collagen fibers & GAG side chains; binding of

    water to (-) charged GAG chains3. Chondronectin promote the adherence of

    chondrocytes to matrix collagen

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    CARTILAGEStructurally, proteoglycans

    resemble bottle brushes:

    *stem protein core

    *bristles GAG chains

    Linking proteins:noncovalently bind coreprotein of PG to linearhyaluronic acid

    Chondroitin sulfate side chains

    of PG electrostaticallybind to the collagen fibrils,forming a cross-linkedmatrixSchematic diagram of a

    cartilage matrix

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    CARTILAGE

    3 MAIN TYPES:(variations in matrix composition)

    1. HYALINE most common;

    matrix: type II collagen

    2. ELASTIC collagen II + elastic fibers

    3. FIBROCARTILAGE

    - weight bearing regions of the body- matrix: dense network of coarse type I

    collagen fibers

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    HYALINE CARTILAGE

    Found in:

    1. Resp. tree up to bronchi

    2. Sternal ends of ribs3. Most articular surfaces of joints

    4. Epiphyseal plates of long bones

    Precursor of bones in the developing

    skeleton

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    HYALINE CARTILAGE

    ROUTINE HISTOLOGIC

    PREPARATIONS collagen not

    demonstrated by light

    microscopy:1. Collagen fibrils have

    submicroscopic dimensions

    2. Similarity of the staining with

    the matrix media3. Almost the same refractive

    index of the collagen fibrils and

    the ground substance

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    HYALINE CARTILAGEPerichondrium- dense CT, covers all hyaline

    cartilage

    - growth & maintenance

    - Collagen I & fibroblasts

    - Layers:

    1. Fibrous mostly collagenous

    fibers & few fibroblasts; merges w/

    subepithelial CT

    2. Chondrogenic more cellular;

    chondroblasts & chondrogenic cell

    Inner Zone strongly basophilic

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    HYALINE CARTILAGE

    Inner Zone

    (Chondrocytes)

    - round

    - lacunae

    - isogenous grps

    - considerable

    shrinkage instandard

    preparations

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    HYALINE CARTILAGE

    Interterritorial matrix

    Territorial / capsular

    matrix

    - rich GAG, less collagen- Basophilic,

    metachromatic

    Inner to outer- Morphologic gradations

    - Peripheral: young

    chondrocytes

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    HYALINE CARTILAGE

    Mature chondrocyte- Small nuclei,

    dispersed chromatin,

    basophilic granular

    cytoplasm

    - Lipid droplets

    - Cytoplasm rich in

    glycogen

    *Active in synthesis of

    both groundsubstance and

    fibrous elements

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    CARTILAGE GROWTH

    Stimulated by:

    1. Growth hormone

    2. Thyroxine3. testosterone

    Retarded by: cortisone, hydrocortisone,estradiol

    Somatotropin somatomedin C acts

    directly on cartilage to promote growth

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    CARTILAGE GROWTH

    2 PROCESSES:

    1. Interstitial growth results from mitotic

    division of isolated chondrocytes to

    form clusters

    2. Appositional growth is the process by

    which cartilage extends its borders;

    occurs when chondroblasts of theperichondrium differentiate into

    chondrocytes

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    CARTILAGE GROWTH

    Interstitial Growth

    - Less important; young cartilage

    - Epiphyseal plates of long bones- Cartilage model (endochondral bone

    formation)

    - W/in articular cartilage (no

    perichondrium)- Becomes less pronounced as matrix

    becomes increasingly rigid from cross-

    linking of matrix components (cartilage

    then grows in girth only by apposition)

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    CARTILAGE NUTRITION

    1. Through the water of solvation of the groundsubstance from capillaries in the perichondrium

    2. Synovial fluid from joint cavities

    *Chondrocytes exhibit low metabolic activity

    limits thickness to which cartilage may develop

    while maintaining viability of the innermost cells.

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    CARTILAGE REGENERATION With difficulty and often incompletely

    FRACTURES: chondroblasts from perichondrium

    invade fractured area & generate new cartilage

    In extensively damaged areas, perichondrium

    generates a scar of dense CT instead of forming

    new cartilage

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    ELASTIC CARTILAGE

    - similar to hyaline cartilage

    except: for bundles of

    branching elastic fibers in

    the matrix

    - Development & growth:interstitial & appositional

    *Found in:

    Ext. ear, EAC, epiglottis, larynx

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    FIBROCARTILAGE

    Intermediate features

    Chondrocytes: singly or in clusters;

    arranged in long rows

    Alternating layers of amorphous matrix

    & coarse type I collagen fibers No identifiable perichondrium

    *Found in:IV disc, articular cart., symph. p.in assoc. w/ dense CT in joint

    capsules, ligaments, tendons

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    BONE

    Composed of cells & collagenous extracellular matrix

    (type I collagen) called OSTEOID, which becomes

    mineralized by the deposition of calcium

    hydroxyapatite

    FUNCTIONS:1. Forms the strong & rigid endoskeleton

    2. Protects the vital internal organs

    3. Acts as reservoir ofCA, PO4 & other ions

    4. Houses the hematopoietic bone marrow

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    BONE

    Special techniques for its preparation:

    < GROUND SECTION

    - does not preserve the

    cells; permit detailed

    study of the matrix,lacunae, canaliculi

    DECALCIFIED BONE

    TISSUE >

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    BONE

    BONE CELLS:

    1. Osteoblasts Synthesize organic matrix

    2. Osteocytes Inactive obsteoblasts trapped in bone

    3. Osteoclasts Multinucleated giant phagocytic cellsimportant in resorption & remodeling of bone tissue

    *Osteoblasts & Osteocytes are derived from a primitive

    mesenchymal cell called OSTEOPROGENITOR

    CELLS

    *Osteoclasts are derived from macrophage-monocyte cell

    line

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    BONE

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    OSTEOBLASTS

    Synthesize osteoid & mediate its

    mineralization

    Lined up along bone surfaces

    Active: cuboidal to columnar; basophiliccytoplasm

    Cytoplasmic processes bring them in contact

    with each other; lacunae & canaliculi appear

    because matrix is formed around them

    Once surrounded by newly synthesized matrix,OSTEOCYTE. This process, BONE

    APPOSITION, is completed by subsequent

    deposition of calcium salts into the newly

    formed matrix

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    OSTEOCLASTS Large, multinucleated, extensively

    branched motile cell containing 5-50(or even more) nuclei

    HOWSHIPS LACUNAE: depressionsresorbed from the bones surface

    RUFFLED BORDER: aspect ofosteoclast in apposition to bone;secretes several organic acids whichdissolve the mineral component whilelysosomal proteolytic enzymes areemployed to destroy the organicmatrix

    CLEAR ZONE: devoid of organelles,yet rich in actin filaments(microfilaments)

    BASAL REGION: nuclei located

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    OSTEOCLASTS Osteoclastic resorption contributes to

    bone remodelling in response togrowth or changing mechanicalstresses upon the bone

    The interactions b/n osteoclasts &osteoblasts are exquisitely regulated

    during normal formation &remodelling of bone

    Osteoclasts also participate in thelong-term maintenance of bloodcalcium homeostasis

    PARATHYROID HORMONE:

    CALCITONIN:

    Stimulatesosteoclastic resorption & release

    Ca ions from bone

    Inhibits osteoclastic

    activity

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    TYPES OF BONE (GROSS)1. Compact (cortical) bone

    dense areas w/o cavities

    2. Cancellous bone(spongy/medullary) areas or

    trabeculae w/ numerousinterconnecting cavities

    *Spongy & compact bone are differentarrangements of the samecomponents; the trabeculae of

    spongy bone consist of a numberof lamellae

    *Sharing the same cavity with thespongy bone is the marrow

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    TYPES OF BONE (Histologic)1. Primary/immature/woven bone - immature

    form w/ randomly arranged

    - formed when ostoblasts produce osteoid rapidly

    (fetal bone devt & adult pathologic rapid new

    bone formation)

    - the rapidly formed woven bone is eventually

    remodelled to form lamellar bone

    - compared to secondary bone:

    lower mineral content

    higher proportion of osteocytes

    2. Secondary/mature/lamellar bone virtually allbone in a healthy adult

    - composed of regular bands of collagenarranged

    in lamellae that are parallel to each other or

    concentrically organized around a vascularcanal

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    PERIOSTEUM & ENDOSTEUM

    *layers of bone-forming cells & CT

    Periosteum external surface of bone

    - richly supplied w/ b.v.

    - Sharpeys fibers: bundles of collagen fibersw/c bind periosteum to underlying bone

    Layers:

    1. Outer fibrous collagen fibers & fibroblasts

    2. Inner, more cellular layer flattened

    osteoprogenitor cells -> mitosis:osteoblasts

    Endosteum internal surface

    - thinner, single layer of flattened

    osteoprogenitor cells, very small amount of CTEndosteum

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    HAVERSIAN SYSTEM (Osteon)The whole complex of concentric bony

    layers or lamellae disposed around a central

    channel containing blood vessels,

    lymphatics, nerves and loose CT

    Canals of Havers or Haversian canals

    Volkmanns canals

    Each Haversian system begins as a broad

    channel. With deposition of successive

    lamellae: dec. diameter of canal,

    osteoblasts trapped as osteocytes in

    lacunae. Osteocytes are thus arranged in

    concentric rings w/in lamellae

    Canaliculicontain fine cytoplasmic

    extensions

    Interstitial systems

    Inner & outer circumferential lamellae

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    HAVERSIAN SYSTEM

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    BONE FORMATION

    1. Intramembranous ossification By direct mineralization of matrix secreted by

    osteocytes

    2. Endochondral ossification By deposition of bone matrix on a pre-existing

    cartilage matrix

    In both processes, the bone tissue that appears

    first is primary or immature

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    Intramembranous

    ossification Source of most flat bones Growth of short bones & thickening of

    long bones

    Occurs w/in membranes of

    condensed primitive mesenchymaltissue. Primary ossification centeris

    the starting point of ossification.

    Anastomosing trabeculae (T) of

    forming bone darkly stained; lighter

    embryonic CT (highly vascular) Bony trabeculae forming primitive

    osteons (Os) surrounding HC

    Osteocytes arranged haphazardly

    Every trabecula covered w/ osteoblasts

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    Intramembranous

    ossificationMesenchymal cells osteoblast synthesize& secrete osteoid at multiple ossificationcenters mineralization of osteoid osteoblasts trapped in lacunae, cytoplasmicextensions in canalicuki. SPICULES formed

    & fuse (spongy bone) remaining CTpenetrated by growing b.v. (Remainingmesenchyme differentiate into bonemarrow)

    osteoprogenitor cells undergo mitotic division,more osteoblasts lay down more bone

    several ossification centers grow radially & finallyfuse together, replacing the original CT

    *The portion of the CT layer that does notundergo ossification gives rise to the endosteum& periosteum of the intramembranous bone

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    Endochondral

    ossification- A small model of solid hyaline cartilage of longbone is 1st formed

    - Perichondrium (w/ osteogenic potential): laysdown bone collar

    - Chondrocytes hypertrophy, resorbingsurrounding cartilage

    - Cartilage matrix calcified, chondrocytes die,leaving large interconnecting spaces

    - Osteogenic bud: invades spaces left

    - Primitive mesenchymal cells differentiate intoosteoblasts; form layer on surface of calcifiedcartilage matrix synthesize bone matrix

    - Calcified cart. matrix resorbed by giant cells

    - BM stem cells from circulation brought byosteogenic bud into forming bone

    - Primary ossification center: accompanied byexpansion of periosteal bone collar

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    Endochondral

    ossification- At the same time, osteoclasts are active;resorption of the bone occurs at the center to

    leave a large medullary space filled w/ bone

    marrow

    - Secondary ossification center in epiphysis:

    growth is radial instead of longitudinal

    *Articular cartilage: does not contribute to bone

    formation

    *Growth or Epiphyseal plate/cartilage: On

    reaching maturity, hormonal changes inhibitfurther cartilage proliferation and the

    epiphyseal plates are replaced by bone,

    causing fusion of diaphysis & epiphysis

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    EPIPHYSIS

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    Epiphyseal CartilageFunctional & Morphologic Zones (from

    epiphyseal side)

    1. RESTING ZONE typical hyaline cartilagew/o morphologic changes in the cell

    2. PROLIFERATIVE ZONE successivemitotic divisions to form columns ofstacked cells

    3. HYPERTROPHIC CARTILAGE ZONE chondrocytes enlarge & becomevacuolated. Matrix is resorbed

    4. CALCIFIED CARTILAGE ZONE Matrix iscalcified

    5. OSSIFICATION ZONE Endochondralbone tissue appears; osteogenic cells &capillaries invade calcified matrix;osteoblasts deposit bone matrix overcalcified cartilage