Factors in Initiation of Ossification

Question 1

Which embryological components form each vertebra?

Answer 1

The caudal half of one somite and the cranial half of the adjacent somite.

Question 2

By which mechanism of ossification do the vertebral centra ossify?

Answer 2

True endochondral

Question 3

By which mechanism of ossification do the neural arches ossify?

Answer 3

Intramembraneous ossification, followed by edochondral ossification.

Question 4

Describe the ossification of the centra

Answer 4

• 1 ossification centre
• Bidirectionally from one area in the lower thoracic / upper lumbar region.
• Around week 9-10

Question 5

Describe the ossification of the neural arches

Answer 5

• 2 ossification centres per arch
• Ossification from 2 areas:
  
  • Lower cervical / upper thoracic
  • Lower thoracic / upper lumbar
• Around week 8

Question 6

Describe the genetic factors initiating ossification

Answer 6

• PAX genes
  
  • There are 9 PAX genes - 1 & 9 found in the VC.
• Responsible for segmentation of the vertebral column and ribs etc.
• Smith et al. (1994) studied fetuses at 7-8 and 10-12weeks
  
  • Found PAX1 in 7-8 weeks but not in 10-12 weeks
• Peters (1999) found that PAX1 and PAX9 have a synergistic effect (double mutant mice had far more issues).
• The notochord signals for induction of PAX1 (removal of notochord leads to a fused cartilaginous tube).

Question 7

What is mechanobiology?

Answer 7

• How a cell reacts to it’s environment by detecting, measuring and responding to external forces.
• Tissue adapts their:
  
  • Function
  • Structure
  • Mass / Density
• This is dependent on their stimuli, but with bone, the structure and density change when exposed to external forces.
  
  • Specifically to bone, these forces are mechanical loading which is essential in skeletal development.

Question 8

Describe mechanotransduction

Answer 8

• Mechanical loading stimulates osteoblasts to lay down new bone.
• Absence of mechanical loading results in osteoclasts reabsorbing bone.

Question 9

What initiates ossification of the neural arch in the cervical region?

Answer 9

The gasp reflex

Question 10

What initiates ossification of the neural arch in the lumbar region?

Answer 10

Muscle twitch due to the limbs developing

Question 11

Bagnall (1977) on initiation of ossification

Answer 11

First to suggest extrinsic factors such as muscle development as an explanation for there being 2 areas of ossification in the neural arches, in particular the cervical / thoracic region in response to the gasp reflex.

Question 12

Land and Schoenau (2008) on initiation of ossification

Answer 12

• Suggested that initiation of ossification in the lumbar area is due to the fetus kicking against resistance in the womb.
  
  • There is a loss of bone mineral density after birth, kicking against no resistance.

Question 13

Van der Meulen (2000) on mechanobiology

Answer 13

• Tested mechanobiology in practice using a group of rats
• Constant strain on the ulna forced remodelling of bone
  
  • This created a new bone in comparison to the control group.
• The bottom line - a cell can change its function based on its external environment (mechanical strain).

Question 14

What are the two processes within skeletogenesis?

Answer 14

1. Histogenesis - differentiation of cells
2. Morphogenesis - controls the formation of shape and size

Question 15

Fetal movements are crucially important in bone development.

Which skeletal problems occur in the absence of these movements?

Answer 15

• Fetal akinesia deformation sequences:
  
  • Thin bones (prone to fractures)
  • Kyphoscoliosis
  • Other spinal problems
  • Joint contractures
• Arthrogryposis
  
  • Joint contractures in 2 or more places
• Developmental dysplasia of the hip (most common):
  
  • Malformed hip joint
  • Partial or full dislocation of the hip joint

Question 16

What is the basic principle of Wolff’s law?

Answer 16

That bone in a healthy person will adapt to the loads under which it is placed.

Question 17

Frost (2003) on Wolff’s law

Answer 17

Stated that the effect of strain was greater than that of stress

Question 18

What happens to bone under mechanical strain?

Answer 18

• Bone mass can be increased or adapted.
• New bone is normally added to areas where there are high strains - this is normally achieved by osteoblasts or osteocytes.

Question 19

What happens to bone with little activity, in those on bed rest and in astronauts?

Answer 19

• Decrease in bone mass and density
  
  • Astronauts experience a reduction in bone mass and density due to the lack of forces acting on the skeleton

Question 20

Rubin et al. (2002) on mechanical stimulation in bone

Answer 20

• Wanted to prove that bone architecture will change without vigorous activity.
• Used low levels of strain to see the effect this had on bone architecture.
• Used 18 sheep - 9 in experimental group and 9 in control group.
• Control group was allowed to roam free.
• Experimental group was oscillated 20 minutes per day 5 times a week - all other times they roamed free.
• Result - mechanical stimuli stimulated bone formation regardless of amount or intensity.

Question 21

What happens when mechanical stimu are absent?

Answer 21

Bone growth is reduced.

Could be due to muscle absence or paralysis

Question 22

Explain the role of muscle contraction in bone growth

Answer 22

• Muscle contraction is vital for normal bone growth
• Even if there is reduced movement, this can alter skeletal development and cause joint formation problems.
• Example - temporary brittle bone diseass (TBBD) - bone fails to form properly in the uterus which then affects the newborn.
  
  • However, mechanical stimulation the bones can return to normal within the first couple of years.
• With muscle paralysis, joint and bone formation are affected.
  
  • Also have poorly defined bone features like condyles and tuberosities.

Question 23

Nowlan et al. (2003) on muscle paralysis and bone formation

Answer 23

Used chick embryos to study the knee joint and paralysis

• Joint A was unmoved - resulted in fusion of the bones (femur and tibia).
• Joint B was moved 5 times per day - clearly developed, normal joint.

Question 24

Explain bone growth concurrent with muscle absence

Answer 24

• Bones will grow regardless of muscle absence
• Similar to muscle paralysis problems:
  
  • Skeletal and joint formation problems
• Problems which can be caused:
  
  • Abnormal curvature of the spine
  • Absent tuberosities
  • Enlarged cervical vertebrae
  • Partial fusing of the cervical vertebrae

Question 25

What happens to the bone formation in the case of neuromuscular disease?

Answer 25

• People with neuromuscular diseases have thinner and weaker bone.
• For example:
  
  • Spinal muscle atrophy
  • Duchenne muscular dystrophy