Oral Health and Prevention Final

Function of Bone

support, mineral storage, hematopoesis

Cancellous Bone

spongy bone in epiphysis of long bones, surrounded by compact bone - has marrow spaces with spicules or trabeculae

bone composition

50% minerals and 50% organic matter (with water) and organic matrix

organic matrix in bone

type I collagen, GAGs, proteoglycans, glycoproteins

Properties of bone

• collagen calcified with with HAP crystals,

• bone reservoir of calcium, phosphate and inorganic ions

• dynamic gain and loss of mineral homeostasis

Osteoblasts histology

cuboidal shape, single nucleus, basophilic, on bone surface

Osteoblast function

secrete organic type 1 collagen and proteins and inorganic minerals (HAP)

Osteoid

unmineralized organic matrix between osteoblasts and mineralized bone

osteocyte histology

squamous, single nucleus, surrounded by mineralized bone matrix

osteocyte location

in lacunae, have cytoplasmic arms in thin channels of bone called canaliculi

osteocyte function

maintain bone

osteoclast histology

large, round, multi-nucleated

Osteoclast location

on bone surface in Howship’s lacunae

Osteoclast function

bone resorption and remodeling (breakdown and removal)

Parts of osteoclasts

• basal zone - contains nuclei & organelles

• ruffled border - finger life projections; active resorption sites

• vesicular zone - transports materials in and out

• clear zone - forms tight seal with bone, isolating resorption area

osteoclast ruffled border

finger like projections (active resorption sites)

• proton pumps (acidifies & decalcifies bone)

• Chloride and water channels (form HCl

• Enzymes degrade organic matrix

• By-products endo/exocytosed into circulation

osteoblast location

cover trabecula surface - secrete osteoid on calcified bone

osteoblasts transformation

can become trapped and transform into osteocytes within lacunae

compact bone

solid bone found around outer edges, circular layers (lamallae) have osteons or Haversian systems

Spongy bone composition

composed of thin plates of bone called bone spicules that surround bone marrow

periosteum

outer fibrous layer with collagen and fibroblasts attached to bone with sharpey’s fibers

blood vessels in bone

enter through nutrient or volkmann’s canals

Osteons

Haversian system - concentric lamallae around a central haversian canal

inner circumferential lamellae

between spongy and compact bone lined by endosteum

outer circumferential lamellae

circle the perimeter of bone

interstitial lamellae

irregular remnants of bone between osteons

lamellae

concentric layers of mineralized bone matrix

lacunae

spaces between lamellae housing osteocytes

canaliculi

tiny channels with osteocyte extensions for communication

haversian canal

central canal of each osteon containing blood and lymphatic vessels and nerves

haversian canals

contain blood vessels and nerves, parallel to the long axis of the osteon and the long axis of the entire bone

volkmanns canals

located at right angles to the haversian canals, vascular channels that connect osteons to eachother, to cancellous bone and to the external cascualr supply of the bone

connective tissue of bone

periosteum - dense irregular connective tissue covering bone, endosteum - loose connective tissue (osteoprogenitor cells) lining all inner bone surfaces

periosteum fibers function to

sharpeys fibers - anchor to bone

tendons and ligaments - connect to bone

Osteogenesis

bone formation through intramembranous or endochondral ossification

intramembranous ossification overview

bone formation from condensed mesenchyme to form mandible, alveolar bone, flat bones (face & skull), clavicles

Endochondral ossification overview

bone formation of hyaline cartilage forming long bones and base of skull.

steps of intramembranous ossification

1. starts in a vascularized mesenchymal membrane

2. mesenchymal cells differentiate into osteoblasts

3. osteoblasts secrete bone matrix forming spicules and trabiculae

4. trabeculae organize into primitive osteons around large haversian canals with blood vessels inside

5. osteocytes are embedded in the matrix and arranged irregularly

6. osteoblasts line every trabecula

7. trabeculae increase and interconnect and their surfaces remain covered by osteoblasts 

Immature (primary) bone formation

1. periosteum develops at bone forming regions

2. osteoblasts beneath periosteum secrete osteoid

3. as osteoblasts get trapped in lacunae, they become osteocytes (more numerous, irregular and larger than in mature bone)

4. collagen fibers are less organized than in mature bone

sequence of intramembranous ossification

1. occurs within an area of vascularized mesenchyme

2. a cluster of mesenchymal cells differentiate into osteoblasts which begin to secrete osteoid

3. osteoblasts are trapped and become osteocytes

4. osteoclasts remodel/shape growing bone

alveolar bone formation

begins in week 8 of development by intramembranous ossification, bone forms directly from the mesenchyme. mesenchymal cells develop into osteoblasts.

What is endochondral ossification and what does it require?

Bone formation that uses a hyaline cartilage model as a template.

The cartilage does not turn into bone—instead, bone is formed on and within it.
This process is responsible for forming most long bones of the body.

What happens when the diaphysis perichondrium becomes vascularized?

Vascularization transforms the perichondrium into a periosteum.
Chondrogenic cells → osteogenic cells, which produce a subperiosteal bone collar by intramembranous ossification.
This collar stabilizes the shaft and is later perforated by osteoclasts so blood vessels can invade.

What occurs in the cartilage center during primary ossification?

Chondrocytes hypertrophy, and their lacunae merge (become confluent).
The cartilage matrix calcifies, cutting off nutrients.
Chondrocytes die, leaving behind spaces for incoming blood vessels and osteogenic cells.

What is the periosteal bud and what does it form?

The periosteal bud (vessels + osteoblasts + osteoclasts) invades the center through the bone collar.
It forms the primary ossification center and a primitive marrow cavity, whose walls consist of a calcified cartilage–bone complex.

What happens in the epiphyses (secondary ossification)?

Secondary ossification centers develop in the epiphyses.
Bone replaces cartilage from the center outward, but the articular cartilage and epiphyseal plate remain.
The plate allows for continued bone growth until adulthood.

What are the mature features of an ossified long bone?

The diaphysis contains spongy bone around a vascular network, deep to a periosteum-lined cortical bone.
The epiphyseal plate remains as a growth zone until it fuses into an epiphyseal line.
Articular cartilage persists at joint surfaces for smooth movement.

stages of bone growth

1. bone collar thickens via osteoblast activity

2. marrow cavity enlarges by osteoclast resorption

3. epiphysis remains as hyaline cartilage while diaphesis forms a bony collar around marrow cavity

secondary ossification

1. appears in epiphyses during later embryonic development

2. hyaline cartilage persists as articular cartilage on epiphyseal surfaces

3. articular cartilage does not contribute to growth

growth in length of bone occurs where

in epiphyseal growth plates of hyaline cartilage

growth in width of bone happens how

by apposition of new bone beneath the periosteum of the bones outer surface

zone of rest (epiphyseal growth plate)

typical hyaline cartilage; provides chondrocytes for continued growth

zone of proliferation (epiphyseal growth plate)

chondrocytes divide, from collumns, secrete cartilage matrix

zones of hypertrophy (epiphyseal growth plate)

chondrocytes enlarge by taking in water and glycogen; matrix is compressed into septae

zones of calcification (epiphyseal growth plate)

chondrocytes degenerate; cartilage matrix calcifies with HAP

zones of ossification (epiphyseal growth plate)

osteoblasts deposit bone on calcified cartilage scaffolds; osteoclasts remodel; mixed spicules (calcified cartilage core & bone matrix coating) form

What maintains the epiphyseal growth plate?

The plate is maintained as long as chondrocyte proliferation (new cartilage formation) and degeneration (cartilage breakdown and ossification) remain balanced.

What happens to chondrocytes in the zone of resting cartilage over time?

They gradually disappear as the plate ossifies and bone growth completes.

At what age do bones typically fuse?

Between ages 12 and 25, depending on the specific bone (earlier in some bones, later in others).

mineralization vs calcification

mineralization is the addition of inorganic crystals to intended locations, calcification happens in locations we don’t want/intend

bone extracellular matrix

inorganic HAP

organic collagen, proteoglycans, glycoproteins

bone cellular components

osteoblasts (osteocytes), osteoclasts, mesenchymal stem cells

Hydroxyapatite

crystals deposited in the gaps formed by the interdigitation of collagen fibers (for structural strength

Mg+ instead of Ca2+ in HAP crystals

inhibits crystal growth

F- instead of OH- in HAP crystals

increases strength by decreasing solubility of crystals

HCO3 instead of HPO4 in HAP crystals

decreases strength by increasing crystal solubility

Osteoblasts derived from

osteoprogenitor cells

Osteoblasts produce

collagen (non-calcified matrix = osteoid)

ground substance (chrondrotin sulfate, glycoproteins)

glycoproteins that osteoblasts produce

osteonectin and osteopontin

osteonectin

initiates mineralization by binding calcium and collagen

osteopontin

anchors osteoclasts to the matrix for resorption by creating a bridge with osteopontin

Macrophage-colony stimulating factor

cytokine that activates the growth and differentiation of osteoclasts (versicles with alkaline phosphatase)

Osteocytes structure

dormant forms of osteoblasts that are linked by canaliculi for transport of nutrients and waste products.

Osteoclasts are derived from

hematopoetic mononuclear cells in the bone marrow

maturation of osteoclasts stimulated by

Macrophage-colony stimulating factor (produced by osteoblasts)

RANK

osteoprotegerin

inhibits osteoclasts differentiation by binding to RANKL and preventing it from binding RANK

three steps of bone formation

• Synthesis of organic and extracellular organic matrix

• matrix mineralization

• bone remodeling

Bone remodeling (time line)

cycles every 4 months,

approx 10% of bone per year,

positive balance before 30yrs,

negative balance after 50 yrs

Phases of bone remodeling

1. resting (quiescent) phase

2. Resorption phase

3. reversal phase

4. formation and mineralization phase (3 mths)

resorption phase of bone remodeling

resorption and differentiation of hematopoetic stem cells into osteoclasts

reversal phase of bone remodeling

transition to bone formation

formation and mineralization phase of bone remodeling

osteoclasts replaced by osteoblasts to initiate bone formation and deposition of osteoid

Dentin composition

70% mineral HAP

20% organic matrix

10% water

organic substances in dentin

collagen

non-collagenous proteins

• DSPP

• Alkaline phosphatase

• glucosaminoglycans, proteoglycans

• growth factors

two steps of dentin formation

1. synthesis of predentin

2. mineralization

synthesis of predentin

ondontoblasts secrete collagen type 1, glucosaminoglycans and DSPP

matrix vesicles in dentin

released from odontoblasts processes

• high concentrations of DSPP with a high affinity for Ca2+

• alkaline phosphatase increases the concentration of phosphates

phosphates + Ca2+ = HAP crystals which grow rapidly and rupture the vessicle

globular mineralization of dentin

crystals form at discrete areas at the same time, growing radially, and fuse (not uniform)

• form mantle dentin

linear pattern of dentin mineralization

uniform mineralization in areas of slow dentin growth - forms long plates

mixt pattern of dentin mineralization

globular and linear mineralization mixed

nucleation sites in extracellular matrix

site where mineralization begins - seeding crystals are released from matrix vesicle

membrane bound vesicles (bone)

contains osteoblasts (initial site of crystal formation), contain Ca2+

rupturing of membrane bound matrix vesicle

accumulation of Ca2+ and PO4 forms calcium phosphate crystals which grow radially to rupture

RANK and RANK L needed for?

for osteoclast formation, differentiation and activation

osteoclast shape

ruffled border on bottom for increased surface area, smooth top

Podosomes and linking proteins function

adhesive ring around the ruffled border of osteoclasts to seal resorptive pit

what happens in resorptive pit

• production of H+ by carbonic anhydrase - acidic environment

• production of iron containing glycoprotein, TRAP - free calcium and phosphate available

• production of cathepsin K to degrade collagen matrix

• production of matrix metalloproteases to degrade inorganic and organic matrix

TNSALP (matrix vesicle)

expressed on the outer membrane of matrix vesicles, hydrolyzes ATP and Pyrophosphate (contributes to HAP formation)

PPi in matrix vesicle

controls rate of mineralization which binds to incipient crystals and limits growth