Lecture Cartilage and Bone

7/29/2019 Lecture Cartilage and Bone

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Cartilage is a specialized form of connective tissue.

Cartilage is composed of cells, chondrocytes (2-5% of the tissue volumeonly) located in lacunae surrounded by an intercellularmatrix.

Cartilage is an avascular tissue with has no blood vessels of its own

Cartilage is a tissue of very low metabolic activity and cell turnover(except in the embryo).

Cartilage receives its nutrients from blood vessels from a surroundingdense connective tissue, the perichondrium.

Nutrients and metabolites pass to and from the cells via the matrix bydiffusion.

Nerves are not present in cartilage, but nerves and nerve ending arepresent in the perichondrium.


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The most important component of cartilage andwhich provides the biomechanical characteristicsof the tissue is the extracellular matrix.

The matrix is composed of amorphous substance inwhich are embedded fibers.

The main components of hyaline cartilage (wetweight) are approximately: Water 72-75%

Proteoglycans 10%

Collagen (type II) 16%

Otherglycoproteins (e.g. chondronectin) 1.6%

Minerals 0.5%


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Cartilage is important for: skeletal support in the embryo

prior to the development of

the bony skeleton.

elongation of developing

long bones (endochondral

ossification).

articulating joints (articular

cartilage).

flexible support in the ear andeartubes, and in the larger

tubes of the respiratory tract

(trachea, bronchi).


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Hyaline cartilage

Elastic cartilage

Fibrocartilage

The difference between thedifferent cartilage types dependon the different properties of the

intercellular matrix, and inparticular on the amount and

type of the fibers embedded inthe matrix.

Cartilageclassification


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Hyaline cartilage is the most common form ofcartilage.

Hyaline cartilage is much more common in theembryo, where it plays an important role in longbone development

Its name is derived from the Greek "hyalos" = glass. Fresh hyaline cartilage is :

a semi-transparent (translucent) milky-white tissue that is both flexible and resilient to mechanical forces.

In adults hyaline cartilage is found in : the respiratory tract (nose, larynx, trachea, bronchi) the ventral part of ribs and on articulating surfaces of long bones and joints

(articular cartilage).


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Elastic cartilage is characterized by its greatflexibility and elasticity owing to the large quantitiesof elastic fibers in the matrix.

Elastic fibers provide the yellowish color in the freshtissue.

The elastic fibers in histological sections can be stained(e.g. with orcein).

The elastic fibers are branched.

The elastic fibers in the matrix near theperichondrium are less-densely packed (and easier

to see) than those deeper in the tissue. Elastic cartilage is found in :

the external ear

in the walls of the external auditory meatus

Eustachian tube

in the epiglottis.


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Fibrocartilage is found in areas of the body subject to highmechanical stress or weightbearing.

It lacks the flexibility of the other cartilage types. Fibrocartilage is present in:

intervertebral disks pubic symphysis temporo-mandibular joints at sites of connection of many ligaments to bones (e.g.

Ligamentum teres femoris) tendon insertions.

Fibrocartilage is characterized by large numbers andconcentrations of collagen fibers in the matrix.

The collagen fibers are the dominant feature of the matrixand with relatively little amorphous matrix.

The large amounts of collagen fibers result in the matrixappearing acidophilic in histological sections after H&Estaining.

Fibrocartilage is not surrounded by perichondrium


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Like all connective tissue,

cartilage is derived in theembryo from mesenchyme.

Mesenchyme cells grow anddifferentiate into young

cartilage cells orchondroblasts,that are very active in secretingthe surrounding matrix.

The chondroblasts grow and

develop in lacunae. These chondroblasts further

differentiate into maturecartilage cells orchondrocytes.


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19PERICHONDRIUM


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Appositional growth describes the addition of new

cartilage cells from the surrounding perichondrium. Flattened cells (chondroprogenitor cells) of the

perichondrium divide and differentiate into ellipticalchondroblasts.

Chondroblasts, are active in secreting the intercellularmatrix.

The chondroblasts typically have basophilic cytoplasm. By transmission electron microscopy the cells are seen to

have well-developed RER and Golgi bodies, typical ofactive secretory cells.

The chondroblasts further differentiate into chondrocytes. The chondrocytes are less basophilic, more rounded and

occupy more rounded lacunae. The amount of matrix surrounding the chondrocytes is

greater than that of the chondroblasts.


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Interstitial growth involves the addition ofcartilage cells by the division of chondrocyteswithin specific lacunae deep in the tissue.

As a consequence of this mitotic activity,lacunae may possess two, four, eight

daughter chondrocytes. These are known as isogenous ornest cells. Interstitial growth is seen in histological

preparations deeper in the older cartilage. Chondrocytes may shrink during histological

preparation and may not occupy the normaldimensions of the lacunae.

This is a preparational artefact.


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Despite the fact that cartilage is foundin relatively few sites in the adult body,its functions are important for our well-being.

Cartilage in adults has very littleregenerative ability if damaged and issubject to tear and wear with aging.

This is due to the dearth of cartilagecells, minimal mitosis, absence of anintegral blood supply and overall lowmetabolic activity of the tissue.

The clinical problems of damage oraging of the tissue (osteoarthritis) aresubstantial.

With aging the cartilage matrix maydevelop calcified deposits (calcifiedcartilage).


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The skeleton is built of bone tissue. Bone provides the internal

support of the body and providessites of attachment of tendonsand muscles, essential forlocomotion.

Bone provides protection for thevital organs of the body: the skullprotects the brain; the ribsprotect the heart and lungs.

The hematopoietic bone marrowis protected by the surrounding

bony tissue. The main store of calcium and

phosphate is in bone. Bone hasseveral metabolic functionsespecially in calciumhomeostasis.


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There are two

main categories

of bone :

1. Spongy bone

(trabecular bone,cancellous bone)

2. Compact bone(cortical bone)


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long bones (e.g.humerus, femur)

flat bones (membranebones)

irregular bones (such asthe vertebrae)

All these bone types,regardless of their

anatomical form, arecomposed of bothspongy and compactbone.


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The main shaft of long bones is called thediaphysis.

At the extremities of the long bone are theepiphyses (in articulating joints).

The region involved in bone elongation betweenthe diaphysis and epiphysis in growing bones iscalled the metaphysis.

The shaft (or diaphysis) is composed of compact(cortical or diaphyseal) bone.

The epiphyses are mainly composed oftrabeculae of spongy bone.

The articulating surface of the epiphyses of

synovial joints is covered with articular cartilage. Bones are covered with a connective tissue

called the periosteum (absent from the articularcartilage surfaces).

A thinner layer of connective tissue, known as theendosteum, surrounds the bone marrow spacesand trabeculae of spongy bone.

The periosteum and endosteum are a source ofnew bone-forming cells (osteoprogenitor cells)and are described as possessing osteogenicpotential.

The periosteum and endosteum are alsoinvolved in bone repair after injury.

Blood vessels of the periosteum and endosteumare involved in nutrition of the bone.


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The flat bones or

"membrane" bones ofthe skull are composedin a sandwich-likefashion of an outer layerof compact bone (outertable), a middle layer ofspongy bone (diploe),and an inner layer ofcompact bone (innertable).

Periosteum covers theflat bone on the outerside (near the scalp)and on the inner side theperiosteum is thicker andcontinuous with theduramater (outermeningeal layer of thebrain).


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The bone matrix has two maincomponents : Organic matrix : The organic matrix is

composed of type I collagen fibers (about

95%) embedded in an amorphous groundsubstance consisting of: sulfated glycosaminoglycans (chondroitin-4-

sulfate, chondroitin-6-sulfate, keratan sulfate)

various bone proteins (bone sialoprotein,

osteocalcin). Inorganic salts : The main calcium deposits

in the bone matrix are in the form of crystalsof hydroxyapatite Ca10(PO4)6.(OH)2


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4 different cell

types are found in

developing bone:

Osteoprogenitorcells

Osteoblasts

Osteocytes Osteoclasts


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Derived from mesenchyme cells.

After birth, flattened, poorly-

differentiated, mesenchyme-like cells,are found in the periosteum andendosteum.

These cells can divide (mitosis) anddifferentiate into bone cells (osteogenicpotential) and as a result are known asosteoprogenitor cells.


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The first cells to develop from the osteoprogenitor cells are theosteoblasts.

Osteoblasts are involved in the formation of bone and are foundon the boundaries of developing and growing bone.

The cells are typically oval, with a large eccentric nucleus, andthe cytoplasm is fairly basophilic.

These cells are very active in synthesizing and secreting thecomponents of the bone matrix and have well-developed rough

endoplasmic reticulum (RER), Golgi bodies and granules. Osteoblasts are rich in the enzyme alkaline phosphatase, which

plays a major role in the formation of the mineral deposits in thematrix.

The collagen fibers are synthesized and secreted by theosteoblasts.


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Osteocytes are mature bone cells thatdevelop from osteoblasts and are located inlacunae within the bony matrix.

Osteocytes have cytoplasmic processeslocated in canaliculi, which penetrate thebony matrix.

Cytoplasmic processes from one osteocytemake contact with the processes fromneighboring osteocytes and cancommunicate via gap junctions.

Because the bony matrix is calcified there isno possibility of diffusion except via thenetwork of canaliculi.


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Osteoclasts are the largest of the bone cells (20-100mm diameter)and are multinuclear (with up to 50 nuclei).

Osteoclasts are involvedin bone resorption and can be found on theeroding surfaces of bone, often in cavities known as Howship'slacunae.

The osteocytic cell membrane closest to the bone undergoingresorption has multiple invaginations and is known as the "ruffledborder".

The cells are metabolically very active, possess large numbers ofmitochondria (resulting in the acidophilia of regular staining) andhave well-developed Golgi bodies.

Osteocytes secrete the enzyme acid phosphatase, which is involvedin the erosion of the bony matrix. (More specifically the enzyme isknown as Tartrate-resistant Acid Phosphatase or TRAP andhistochemical localization of TRAP enzymatic activity is a usefulmarker for identifying osteoclasts in sections).

Osteoclasts originate from monocytes and are included in the

mononuclear phagocyte system.


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The resorption of osteons involves osteoclasts from theHaversian canals eroding parts of lamella leading to theformation of resorption cavities.

These may connect with resorption cavities from adjacentosteons.

When sufficient resorption has occurred, osteoblasts appearin the resorption cavity and start building a new generationof osteons.

When the new osteon is completed, the remnants of theprevious osteon result in an interstitial system.

This process of remodeling continues throughout life.


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Intramembranous ossification occurs


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Intramembranous ossification occursduring the embryonic developmentof many flat bones of the skull("membrane bones") and jaw.

During the initial stages of theprocess there is a proliferation andaggregation of mesenchyme cells,and simultaneously in the area onefinds the development of manysmall blood vessels.

The long processes of themesenchyme cells are in contactwith those of neighboringmesenchyme cells.

The mesenchyme cells begin tosynthesize and secrete fine collagen

fibrils and an amorphous gel-likesubstance into the intercellularspaces.

This is followed by the differentiationof the mesenchyme cells intoosteoblasts (identified by theirbasophilia and eccentric nuclei).

The osteoblasts synthesize andsecrete the components of the

osteoid (prebone) which, at a laterstage, becomes calcified resulting inthe development of bone spicules ortrabeculae.

Primitive blood vessels are seen inthe connective tissue locatedbetween the trabeculae. At a laterstage the connective tissuesurrounding the developing flat

bone forms the periosteum.


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Endochondral ossification is best illustrated in the developing long

bones. The first stages involve the development of a hyaline cartilage

model with surrounding perichondrium. A layer of woven bone (the periosteal collar) develops around the

central shaft of the cartilage as a result of intramembranous ossification.

Primary (diaphyseal) center of ossification. The chondrocytes in the developing central sha(primary center of

ossification) hypertrophy (enlarge with swollen cytoplasm) and theirlacunae also become enlarged.

The intercellular matrix becomes calcified.

As a result, there is no diffusion via tmatrix and the chondrocytesdegenerate and die, leaving a network of calcified cartilage.

At the same time, blood vessels and mesenchyme-like cells from theperiosteum penetrate this region of the diaphysis.

Osteoblasts differentiate from the mecells and begin forming primarybone tissue on the calcified cartilage framework

A bone marrow cavity forms in the developing diaphysis as a resultof osteoclastic activity eroding the primary spongy bonetrabeculae. The bone cavity enlarges accompanied by further vascularization.

The further elongation of long bones occurs in the growth plates of the

metaphysis.

Stages of Endochondral


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Stages of Endochondral

Ossification


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resting zone (small flattened

lacunae) zone of proliferation (site of mitoses,

and larger elliptical lacunae) zone of hypertrophy (greatly

enlarged and rounded

chrondrocytes in enlarged lacunae) zone of calcification of the matrix

and degeneration of thechondrocytes

zone of ossification. Osteoblasts areinvolved in forming bone trabeculaeon the remains of the calcified

cartilage. primary spongiosa (primary spongy

bone) where the newly-formedtrabeculae are continuously beingeroded by osteoclastic activity andremodelled


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Stress fracture causedby trauma car accident, fall,

athletics, etc

Pathological fracture

in bone weakened bydisease bone cancer or

osteoporosis

Fractures classified by

structuralcharacteristics break in the skin multiple pieces


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Normally 8 - 12 weeks(longer in elderly)

Stages of healing fracture hematoma (1) -

clot forms, then osteogeniccells form granulation

tissue soft callus (2)

fibroblasts produce fibersand fibrocartilage

hard callus (3) osteoblasts produce a

bony collar in 6 weeks

remodeling (4) in 3 to 4months spongy bone replaced by

compact bone


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F t l Sk l t t 12 W k


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Fetal Skeleton at 12 Weeks


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Lecture Cartilage and Bone