Development and Normal Structure / Function of Bones

Question 1

What type of mesoderm forms the somites? What portion develops into the skin / spinal column?

Answer 1

Paraxial mesoderm

Dorsal portion - dermatomyotome, becomes axial muscles and skin

Ventral portion - sclerotome, develops into annulus fibrosis of vertebral column

Question 2

What forms the limb bud + its skin? When does it form?

Answer 2

Limb bud formed by lateral plate mesoderm

Covered by ectoderm on apical ectodermal ridge

Forms around 4th week the upper limb bud, then 2 days later the lower limb bud

Question 3

What is meant by resegmentation of the sclerotome? Where will the arteries and nerves be?

Answer 3

Caudal portion of each sclerotome (derived from a somite) migrates downward to join the cranial portion of the subjacent sclerotome

• > spinal nerve roots interacting with the myotome will peak through these new divisions
• > arteries will be formed in the center of the new vertebral bodies

Question 4

How does syndactyly occur?

Answer 4

If apical ridges forming the digital rays are not properly divided by apoptosis

Question 5

What are the genes which control the organization of the embryo and what happens if it goes wrong?

Answer 5

Homeobox (Hox) genes -> segmentation and orientation of the embryo in a craniocaudal direction.

If mutated -> appendages in wrong locations

Question 6

What are the AER and ZPA and what do they secrete?

Answer 6

AER - apical ectodermal ridge - secrete fibroblast growth factor to stimulate the underlying mesenchyme to proliferate, controls proximal-distal axis of limb bud (induces lengthening)

ZPA - zone of polarizing activity, at base of limb bud (pinky side), secretes sonic hedgehog, controls anteroposterior axis of limb bud differentiation (his spikes are sharp and polarizing)

Question 7

What gene is mutated in holoprosencephaly?

Answer 7

Sonic hedgehog gene -> also needed for CNS development. Disrupted in trisomy 13

Question 8

What utilizes the Wnt-7 gene and what does it do?

Answer 8

Released by AER (in conjunction with FGF). Controls the dorsal-ventral axis of the limb buds.

Question 9

How are the joints developed? What does it require of the fetus?

Answer 9

Mesenchyme condenses, with cleft formation and cavitation.

Normal development requires fetal motion in utero

Question 10

What types of bone are best at resisting compression / bending?

Answer 10

Spongy bone -> best at resisting compression (i.e. what’s found mostly in the vertebral column)

Compact bone -> best are resisting bending -> i.e. what’s found in the diaphysis of the humerus

Question 11

What is spongy bone also called, and why is it more metabolically active than compact bone? Where can it be found in long bones?

Answer 11

Also called cancellous, trabecular, or medullary bone

More metabolically active because it has a much larger surface area -> all covered with endosteum which is constantly turning over

Can be found in the head of long bones since those need to resist compression from pressing in the joint

Question 12

What type of bones make up the skull?

Answer 12

Flat bones - two layers of compact gone with a thin layer of cancellous bone inbetween

Question 13

What is the definition of growth plate and metaphysis?

Answer 13

Growth plate -> thin layer of cartilage between primary and secondary ossification centers - “physis”

Metaphysis -> closer to the diaphysis than the growth plate is, it is the region just below the growth plate (or above if more distally)

Question 14

What are the two layers of the periosteum?

Answer 14

1. Outer thin fibrous layer, containing dense irregular connective tissue and fibroblasts
2. Inner layer contacting surface of the bone, contains osteoprogenitor cells giving ride to osteoblasts

Question 15

How do tendons anchor into bone?

Answer 15

Sharpey’s fibers (Type 1 collagen) penetrate the periosteum and attach directly to bone.

Question 16

What is the morphology of the collagenous portion of osteoid?

Answer 16

Fibrils - stacks of triple helical collagen molecules aligned in a staggered array

Fibers - bundles of fibrils together, resists pulling

Question 17

What are the noncollagenous proteins within the osteoid?

Answer 17

1. Adhesion proteins - i.e. osteopontin
2. Mineralization protein and calcium binding proteins - osteocalcin and osteonectin
3. Enzymes - alkaline phosphatase
4. Cytokines / growth factors -> will stimulate osteoblasts during bone breakdown by osteoclasts

Question 18

Which cell of the bone looks alot like plasma cells when activated? What is the name of the layer that it lays down?

Answer 18

Osteoblasts -> abundant ER to make collagen protein

Osteoid seam -> think layer of nonmineralized bone matrix, generally around 10 microns thick.

Question 19

What cell coordinates the bone remodelling shape?

Answer 19

Osteocytes -> communicate by small canaliculi to coordinate whats going on

Question 20

How do osteoclasts look and how do they interact with the bone?

Answer 20

They look like multinucleated giant cells in bone

They interact with the bone surface via the ruffled border -> forms a tight seal with microvilli

Forms Howship’s lacunae

Question 21

Describe the progress by which most flat, non-weight bearing bones are formed (i.e. skull, clavicles)?

Answer 21

Intramembranous ossification
-> aggregation of mesenchyme into osteoblasts.

formation of bone spicules which coalesce into woven bone

There is no cartilage precursor in this type. The woven bone will eventually reform into mature, lamellar bone by remodelling.

Question 22

What is the secondary ossification center of bone formation? What is between the primary and secondary ossification center?

Answer 22

Spot in the epiphyses where bone begins to form, so it can make spongy bone.

Been primary and secondary ossification center is the growth plate.

Question 23

What is the progression of cells at the growth plate during bone formation?

Answer 23

1. Zone of reserve cartilage (closer to epiphysis)
2. Zone of proliferation -> longitudinal columns of chondrocytes
3. Zone of hypertrophy -> hypertrophy of condrocytes
4. Zone of degeneration -> dying chondrocytes (apoptosis) with calcification of cartilage matrix
5. Zone of ossification -> in the metaphysis, where vessels and boneforming cells invade and deposit immature bone matrix over cartilage remnants.

Question 24

How does final ossification of the growth plate affect infection susceptibility?

Answer 24

Allows infections of the diaphysis/metaphysis to spread into the epiphysis, as vascular continuity is established at puberty when the growth plate closes.

Before this, infection cannot spread to the metaphysis because cartilage is avascular.

Question 25

What is meant by appositional growth of bone?

Answer 25

Bone can only grow on the surface of a pre-existing substrate such as bone or calcified cartilage.

Question 26

How do the osteocytes appear differently between woven bone and lamellar bone?

Answer 26

Woven -> closely crowded, oriented randomly, and plump / round

Lamellar (mature) -> uniformly spaced, less crowded, regularly oriented, flat

Question 27

When is immature (woven bone) seen?

Answer 27

Development, active bone growth / repair (i.e. fracture repair), and pathologic conditions

Question 28

What does the matrix look like in woven bone vs lamellar bone?

Answer 28

Woven - irregularly arranged, and more basophilic

Lamellar - arranged in layers, collagen alternating direction between layers (peripendicular between layers within an osteon). Also looks much more acidophilic

Question 29

Do canaliculi cross cement lines?

Answer 29

NO -> cement lines are the line indicating the edge of the osteon (space dug out by osteocytes). Only osteocytes within a given osteon will communicate.

Cement lines are the outermost refractive layer of an osteon.

Question 30

What are Haversian / Volkmann’s canals and why aren’t they seen in spongy bone?

Answer 30

Haversian canals - longitudinal blood vessels

Volkmann’s - transverse blood vessels

Not seen in spongy bone because the blood supply / vasculature has much easier access since it is thin and perforated.

These two structures are only seen in lamellar (mature) cortical bone.

Question 31

What are interstitial and circumferential lamellae?

Answer 31

Interstitial lamellae - lamellae between osteons

Circumferential lamellae:

1. Periosteal large rings on outside of cortical bone (periosteal) -> where Sharpey’s fibers anchor
2. Endosteal large rings