Factors in Initiation of Ossification Flashcards
Which embryological components form each vertebra?
The caudal half of one somite and the cranial half of the adjacent somite.
By which mechanism of ossification do the vertebral centra ossify?
True endochondral
By which mechanism of ossification do the neural arches ossify?
Intramembraneous ossification, followed by edochondral ossification.
Describe the ossification of the centra
- 1 ossification centre
- Bidirectionally from one area in the lower thoracic / upper lumbar region.
- Around week 9-10
Describe the ossification of the neural arches
- 2 ossification centres per arch
- Ossification from 2 areas:
- Lower cervical / upper thoracic
- Lower thoracic / upper lumbar
- Around week 8
Describe the genetic factors initiating ossification
- 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).
What is mechanobiology?
- 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.
Describe mechanotransduction
- Mechanical loading stimulates osteoblasts to lay down new bone.
- Absence of mechanical loading results in osteoclasts reabsorbing bone.
What initiates ossification of the neural arch in the cervical region?
The gasp reflex
What initiates ossification of the neural arch in the lumbar region?
Muscle twitch due to the limbs developing
Bagnall (1977) on initiation of ossification
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.
Land and Schoenau (2008) on initiation of ossification
- 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.
Van der Meulen (2000) on mechanobiology
- 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).
What are the two processes within skeletogenesis?
- Histogenesis - differentiation of cells
- Morphogenesis - controls the formation of shape and size
Fetal movements are crucially important in bone development.
Which skeletal problems occur in the absence of these movements?
- 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
What is the basic principle of Wolff’s law?
That bone in a healthy person will adapt to the loads under which it is placed.
Frost (2003) on Wolff’s law
Stated that the effect of strain was greater than that of stress
What happens to bone under mechanical strain?
- 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.
What happens to bone with little activity, in those on bed rest and in astronauts?
- 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
Rubin et al. (2002) on mechanical stimulation in bone
- 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.
What happens when mechanical stimu are absent?
Bone growth is reduced.
Could be due to muscle absence or paralysis
Explain the role of muscle contraction in bone growth
- 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.
Nowlan et al. (2003) on muscle paralysis and bone formation
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.
Explain bone growth concurrent with muscle absence
- 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
What happens to the bone formation in the case of neuromuscular disease?
- People with neuromuscular diseases have thinner and weaker bone.
- For example:
- Spinal muscle atrophy
- Duchenne muscular dystrophy
