Development and Normal Structure / Function of Bones Flashcards
What type of mesoderm forms the somites? What portion develops into the skin / spinal column?
Paraxial mesoderm
Dorsal portion - dermatomyotome, becomes axial muscles and skin
Ventral portion - sclerotome, develops into annulus fibrosis of vertebral column
What forms the limb bud + its skin? When does it form?
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
What is meant by resegmentation of the sclerotome? Where will the arteries and nerves be?
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
How does syndactyly occur?
If apical ridges forming the digital rays are not properly divided by apoptosis
What are the genes which control the organization of the embryo and what happens if it goes wrong?
Homeobox (Hox) genes -> segmentation and orientation of the embryo in a craniocaudal direction.
If mutated -> appendages in wrong locations
What are the AER and ZPA and what do they secrete?
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)
What gene is mutated in holoprosencephaly?
Sonic hedgehog gene -> also needed for CNS development. Disrupted in trisomy 13
What utilizes the Wnt-7 gene and what does it do?
Released by AER (in conjunction with FGF). Controls the dorsal-ventral axis of the limb buds.
How are the joints developed? What does it require of the fetus?
Mesenchyme condenses, with cleft formation and cavitation.
Normal development requires fetal motion in utero
What types of bone are best at resisting compression / bending?
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
What is spongy bone also called, and why is it more metabolically active than compact bone? Where can it be found in long bones?
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
What type of bones make up the skull?
Flat bones - two layers of compact gone with a thin layer of cancellous bone inbetween
What is the definition of growth plate and metaphysis?
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)
What are the two layers of the periosteum?
- Outer thin fibrous layer, containing dense irregular connective tissue and fibroblasts
- Inner layer contacting surface of the bone, contains osteoprogenitor cells giving ride to osteoblasts
How do tendons anchor into bone?
Sharpey’s fibers (Type 1 collagen) penetrate the periosteum and attach directly to bone.
What is the morphology of the collagenous portion of osteoid?
Fibrils - stacks of triple helical collagen molecules aligned in a staggered array
Fibers - bundles of fibrils together, resists pulling
What are the noncollagenous proteins within the osteoid?
- Adhesion proteins - i.e. osteopontin
- Mineralization protein and calcium binding proteins - osteocalcin and osteonectin
- Enzymes - alkaline phosphatase
- Cytokines / growth factors -> will stimulate osteoblasts during bone breakdown by osteoclasts
Which cell of the bone looks alot like plasma cells when activated? What is the name of the layer that it lays down?
Osteoblasts -> abundant ER to make collagen protein
Osteoid seam -> think layer of nonmineralized bone matrix, generally around 10 microns thick.
What cell coordinates the bone remodelling shape?
Osteocytes -> communicate by small canaliculi to coordinate whats going on
How do osteoclasts look and how do they interact with the bone?
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
Describe the progress by which most flat, non-weight bearing bones are formed (i.e. skull, clavicles)?
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.
What is the secondary ossification center of bone formation? What is between the primary and secondary ossification center?
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.
What is the progression of cells at the growth plate during bone formation?
- Zone of reserve cartilage (closer to epiphysis)
- Zone of proliferation -> longitudinal columns of chondrocytes
- Zone of hypertrophy -> hypertrophy of condrocytes
- Zone of degeneration -> dying chondrocytes (apoptosis) with calcification of cartilage matrix
- Zone of ossification -> in the metaphysis, where vessels and boneforming cells invade and deposit immature bone matrix over cartilage remnants.
How does final ossification of the growth plate affect infection susceptibility?
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.
What is meant by appositional growth of bone?
Bone can only grow on the surface of a pre-existing substrate such as bone or calcified cartilage.
How do the osteocytes appear differently between woven bone and lamellar bone?
Woven -> closely crowded, oriented randomly, and plump / round
Lamellar (mature) -> uniformly spaced, less crowded, regularly oriented, flat
When is immature (woven bone) seen?
Development, active bone growth / repair (i.e. fracture repair), and pathologic conditions
What does the matrix look like in woven bone vs lamellar bone?
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
Do canaliculi cross cement lines?
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.
What are Haversian / Volkmann’s canals and why aren’t they seen in spongy bone?
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.
What are interstitial and circumferential lamellae?
Interstitial lamellae - lamellae between osteons
Circumferential lamellae:
- Periosteal large rings on outside of cortical bone (periosteal) -> where Sharpey’s fibers anchor
- Endosteal large rings
