1 bch 443 biochemistry of specialized tissues 3. cartilage, bone & teeth tissue

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BCH 443BCH 443Biochemistry of Biochemistry of

Specialized TissuesSpecialized Tissues

3. Cartilage, Bone & Teeth Tissue3. Cartilage, Bone & Teeth Tissue

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Types of Connective Tissue Found in the Skeletal System

Cartilage Bone

Each of these connective tissue types consists of: living cells, nonliving intercellular protein fibers, an amorphous (shapeless) ground substance

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Cartilage

Location Ear and nose Respiratory system Movable joints Costal cartilage Intervertebral disks Pubic symphysis Embryonic

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Cartilage Tissue

Specialized CT Chondrocytes in lacunae Solid ground substance and fibers Avascular No nerves Perichondrium 60-80% water –

resilient

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Hyaline Cartilage

Most abundant Locations

Joints Trachea Costal cartilages

Network of collagen fibers

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Elastic Cartilage

Elastic fibers Locations

External ear Epiglottis

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Fibrocartilage

Bundles of collagen fibers in rows Locations

Intervertebral disks Pubic symphysis Menisci

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Cartilage: Function

articular (or hyaline) cartilage covers bone surfaces within the joint capsule

basic functions: lubrication prevents wear despite common belief does not serve as a

“shock absorber” very thin capacity negligible compared to muscles and

bones functions within a contact pressure range

of 2-11 MPa

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Cartilage: Composition

Water+proteoglycan+collagen+ions

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water contains dissolved inorganic salts tissues with high proteoglycan content

high water content low hydraulic permeability high compressive stress damage to proteoglycans will result in

increased water mobility and impaired mechanical function

void (i.e. pore) dimension 50Å!

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interaction between chemical and mechanical factors pH (potential of hydrogen, -log10[H+])

will affect numbers of negative charge groups change in bound water and mobility

cations shields proteoglycan charges change in bound water and mobility

5% of tissue volume is chondrocytes

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Cartilage: Structure

Split line patterns (preferred collagen fiber orientation)

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Superficial zone densely packed

collagen fibrils organized parallel

to articular surface oblong

chondrocytes Middle zone

fibers more or less randomly arranged

greater fiber diameter

round cells

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Deep zone Cells

arranged in columns along the radial direction

Calcified cartilage and subchondral bone

large fibers from the deep zone anchor into this region

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Collagen orientation parallel to the surface on the superficial

layer oblique in the middle layer perpendicular to the surface in the

deep zone Proteoglycan content

increases from surface till the middle zone and diminishes towards the deep zone

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Water proteoglycans can hold water up to 50

times their weight 70% of the water is bound to

proteoglycans remaining 30% bound to collagen inorganic ions such as Ca, Na, Cl and K

are dissolved balance fixed charges on proteoglycans

and generate swelling pressure

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proteoglycan-proteoglycan interactions aggregation

entropically favored cations are attracted to maintain

electroneutrality resulting in osmotic swelling pressure (0.35 MPa)

negative charges on the GAG chains exert electrostatic repulsive forces on one another

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Aggregated Proteoglycans

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A Rabbit’s Mojo and Proteoglycans…

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collagen-proteoglycan interactions

interactions involve mechanical

entanglement electrostatic bonds

negative charges of GAGs and protein core bind to collagen

excluded volume effects a given molecule inhibits

neighboring molecules from interacting with the water in its hydrodynamic domain

prevents proteoglycans from passing in to solution (PGs are water soluble)

balance and resist the internal swelling forces of proteoglycans

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Cartilage: Properties

ultimate tensile strain varies from 60% to 120%

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Bone

Definition Connective tissue in which the

intercellular matrix has been impregnated with inorganic calcium salts

Has great tensile and compressible strength but is light enough to be moved by coordinated muscle contractions

Composition Two types of substances—organic matter

and inorganic salts

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Bone Functions

Support body weight Protect soft organs Movement at joints Storage of Ca++ and PO4

-3

Hematopoiesis

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Bone Composition

35% cells, fibers (collagen), ground substance

65% mineral salts, mainly calcium phosphate precipitated around collagen fibers

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Types of Bone

Cancellous (spongy) bone Found in the interior of bones Composed of trabeculae, or spicules, of

bone that form a lattice-like pattern Compact (cortical) bone

Forms the outer shell of a bone Has a densely packed calcified

intercellular matrix that makes it more rigid than cancellous bone

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Types of Bone Cells

Osteogenic cells Osteoblasts Osteocytes Osteoclasts

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Bone Formation

Osteogenesis – development of the skeleton and growth through adolescence (~18 females, ~21 males)

Osteoblasts secrete osteoid Osteoid is mineralized (calcium phosphate

precipitates) Osteoblasts become osteocytes Forms woven bone (immature) Periosteum formed Mature lamellar bone formed on surfaces

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Bone Growth

Regulated by: Growth hormone Thyroid hormone Sex hormones

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Actions of Parathyroid Hormone

Increases intestinal absorption of calcium Increases intestinal absorption of

phosphate Decreases renal excretion of calcium Increases renal excretion of phosphate Increases bone resorption Decreases bone formation Promptly increases serum calcium levels Prevents increase in serum phosphate

levels

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Action of Calcitonin

Increases renal excretion of phosphate Increases renal excretion of calcium Decreases bone resorption Decreases serum calcium levels with

pharmacologic doses Decreases serum phosphate levels with

pharmacologic doses

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Action of Vitamin D

Increases intestinal absorption of calcium Increases intestinal absorption of

phosphate Increases renal excretion of phosphate Can increase bone resorption Can increase bone formation

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Classification of Bones

Long bones Found in the upper and lower extremities

Short bones Irregularly shaped bones located in the

ankle and the wrist Flat bones

Composed of a layer of spongy bone between two layers of compact bone

Found in areas such as the skull and rib cage

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Demineralization of enamel

Ca10(PO4)6(OH)2 + 2 H+ --> 10Ca2+ + 6 PO43- + 2 H2O

HYDROXYAPATATITE(solid)

Dissolved ions

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Tooth decay process

Bacteria in mouth convert sugars to polysaccharides

Plaque = coating of bacteria + polysaccharides

Other bacteria convert the carbohydrates in plaque to carboxylic acids such as lactic acid

Tartar = plaque that combines with Ca2+ and PO4

3- ions in saliva to form a hard yellow solid

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Protection of enamel by fluoride

Ca10(PO4)6(OH)2 + 2 F- --> Ca10(PO4)6(F)2 + 2 OH-

HYDROXYAPATATITE(solid)

FLUOROAPATATITE(solid)

Ca10(PO4)6(F)2 + 2 H+ --> no reaction

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Chemical Composition of Bone

Bones composed of Organic matrix and Inorganic mineral componentOrganic (35%): structure, flexibility, tensile strength, resists stretching

and twisting Cells

osteocytes osteoblasts osteoclasts

Osteoid

Inorganic (65%): hardness, strength, durability, resists compression and tension

Hydroxyapatite (mineral salts) Storage for Ca, P, Su, Mg, Cu

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Regulation of Bone Growth

Vitamin C (ascorbic acid): Lack of vitamin C leads to

poor structure, less effective support, swollen & painful connective tissues. Wounds heal poorly (scar tissue is rich in collagen fibers). Gums bleed as connective tissue around teeth weakens

Scurvy is the vitamin C deficiency disease

White line of Frankl: dense band in metaphysis Wimberger’s ring: small epiphysis with sclerotic ring Subperiosteal hemorrhage Most common: Distal end of femur, proximal & distal tibia &

fibula, distal radius & ulna, proximal humerus, sternal ends of ribs

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Regulation of Bone Growth (Con’t)

Vitamin D 7-dehydrocholesterol located in the

skin: forms in the presence of ultraviolet light

Becomes Vit. D3 (cholecalciferol) in liver, Calcidiol in kidney

Calcitriol hormone + parathyroid: stimulates bone deposition, reduced excretion of Ca+ and increased absorption of Ca+ from gut

Vitamin D 7-dehydrocholesterol located in the

skin: forms in the presence of ultraviolet light

Becomes Vit. D3 (cholecalciferol) in liver, Calcidiol in kidney

Calcitriol hormone + parathyroid: stimulates bone deposition, reduced excretion of Ca+ and increased absorption of Ca+ from gut

Deficiency: Osteomalacia is bone degeneration (similar to rickets) in the

elderly, who stay out of the sun. Rickets is a softening and weakening of childrens’ bones

Calcification slows at epiphyses Growth plate widens and appears frayed and cupped Bones bend from stresses of weight bearing Reduction in cortical bone density

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Vitamin A Retinol easist for the body to use. Found in animal foods (liver, eggs and

fatty fish). Beta-carotene is a precursor for vitamin A. The body needs to convert it to retinol or vitamin A for use. Found in plant foods (orange and dark green veggies: carrots, sweet potatoes, mangos and kale).

The body stores both retinol and beta-carotene in the liver, drawing on this store whenever more vitamin A is needed.

Stimulates osteoblast activity, needed for cell division. Too much vitamin A linked to bone loss and increased risk of hip

fracture. Excessive amounts of vitamin A triggers an increase in osteoclasts and it may also interfere with vitamin D

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Vitamin B-12 found in animal products (meat, shellfish, milk, cheese and eggs) Important for blood formation and clotting Low levels linked to loss of bone mass However deficiency is uncommon in younger women who are also at

less risk of osteoporosis

Vitamin K Important for protein synthesis in bone Low intake of Vitamin K associated with osteopenia (reduction of bone

mass) and osteoporotic fracture (only in women?)

Calcium, Magnesium, Phosphorous, Potassium

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Regulation of Bone growth (Con’t)

Hormones chemicals produced by the endocrine glands and secreted directly into the

bloodstream to their target organs to control the activity of that organ.. Can stimulate cartilage formation, Vitamin D production, cause the release

of Ca & P from bone, and sex hormones play a role in the termination of long bone growth

Estrogen: rapid and early growth Androgens: later, slower growth

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Hormonal Mechanism

Rising blood Ca2+ levels trigger the thyroid to release calcitonin

Calcitonin stimulates calcium salt deposit in bone

Falling blood Ca2+ levels signal the parathyroid glands to release PTH

PTH signals osteoclasts to degrade bone matrix and release Ca2+ into the blood

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Hormonal Mechanism

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Modified calcium phosphates in the biological system of

humansFormula Occurrences

(Ca,Z)10(PO4,Y)6(OH,X)2 HAp enamel, dentine, bone, dental calculi, stones, urinary calculi, soft tissue calcifications

Ca8H2(PO4)6·5H2O OCP dental and urinary calculi

CaHPO4 ·2H2O DCPD dental calculi, chondrocalcinosis, crystalluria, decomposed

(Ca,Mg)9(PO4)6 TCP dental and urinary calculi, salivary stones, dentinal caries, arthritic cartilage, soft tissue calcification

(Ca,Mg)?(PO4,Q)? ACP soft tissue calcification

Ca2P2O7·2H2O CPPD pseudo-gout deposits in synovium fluids

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Dentin

Enamel

Dentinal Tubules

CementumPulp

Alveolar ProcessCortical Plate

Spongy Bone

Periodontal Ligaments

Gingiva

Tooth Structure

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Tooth Structure

Two main regions – crown and the root Crown – exposed part of the tooth above

the gingiva (gum) Enamel – acellular, brittle material

composed of calcium salts and hydroxyapatite crystals is the hardest substance in the body Encapsules the crown of the tooth

Root – portion of the tooth embedded in the jawbone

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a. Enamel (1) Makes up anatomic crown. (2) Hardest material in the human body. (3) Incapable of remodeling and

repair.

Tooth Structure (Con’t)

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b. Dentin(1) Makes up bulk of tooth.

(2) Covered by enamel on crown and cementum on the root.

(3) Not as hard as enamel.(4) Exposed dentin is often

sensitive to cold, hot, air, and touch (via dentinal tubules).


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c. Cementum (1) Covers root of tooth. (2) Overlies the dentin and joins

the enamel at the cemento- enamel junction (CEJ).

(3) Primary function is to anchor the tooth to the bony

socket with attachment fibers.


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d. Pulp (1) Made up of blood vessels and nerves entering through the

apical foramen. (2) Contains connective tissue,

which aids interchange between pulp and dentin.


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Tooth and Gum Disease

Dental caries – gradual demineralization of enamel and dentin by bacterial action Dental plaque, a film of sugar, bacteria,

and mouth debris, adheres to teeth Acid produced by the bacteria in the

plaque dissolves calcium salts Without these salts, organic matter is

digested by proteolytic enzymes Daily flossing and brushing help prevent

caries by removing forming plaque

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Tooth and Gum Disease: Periodontitis

Gingivitis – as plaque accumulates, it calcifies and forms calculus, or tartar

Accumulation of calculus: Disrupts the seal between the gingivae

and the teeth Puts the gums at risk for infection

Periodontitis – serious gum disease resulting from an immune response

Immune system attacks intruders as well as body tissues, carving pockets around the teeth and dissolving bone

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Proposed Mechanisms of Action of Fluoride

enamel resistance to acid demineralization.

rate of enamel maturation after eruption. Remineralization of incipient lesions

at the enamel surface. >1ppm fluoride needed to slow

demineralization process. Interference with microorganisms Improved tooth morphology.

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How Does Dental Caries Begin?

Formation of acid by microorganisms in plaque overly the enamel.

Requires the simultaneous presence of three factors: (1) microorganisms, (2) a diet for the microorganisms, (3) a susceptible host or tooth surface.

If (1-3) are absent = no caries.

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Remineralization

Remineralization: deposition of calcium, phosphate, and other ions into areas of previously demineralized by caries or other causes.

Porous or slightly demineralized enamel has a greater capacity to acquire fluoride than adjacent sound enamel (3-5x more!)

Greater capacity of demineralized enamel to absorb fluoride. = enamel dissolution

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Biochemical Basis

Enamel exposed to pH of 5.5 = enamel

dissolution:

Ca10(PO4)6(OH)2 + 8 H+

10 Ca++ + 6HPO2-4 + 2 H2O

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Biochemical Basis (Con’t)

Fluoride exposure reduces enamel solubility when fluorapatite is formed.

Ca10(PO4)6(OH)2 + 2 F-

Ca10 (PO4)6F2 + 2 OH-

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Demineralization and Remineralization

Caries dissolution of enamel

cyclic phenomenon with phases of

demineralization and reprecipitation.

Determined by changes in pH and ionic

concentrations within the plaque and the

lesion.

1 bch 443 biochemistry of specialized tissues 3. cartilage, bone & teeth tissue

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