Factors In Initiation Of Ossification Flashcards
What is bone derived from?
Mesenchyme
What is the process of intramembranous ossification? (Reference?)
- Mesenchyme becomes highly vascularised
- Some cells differentiate into osteoblasts and deposit osteoid
- Osteoblasts become trapped and become osteoclasts
- Organisation -> eg. Haversian systems around blood vessels
- Osteoblasts remain at periphery and lay down lamellae
- Osteoclasts keep centre speculated/spongy
(Moore and Persaud, 2008)
Where does intramembranous ossification occur?
Within a membranous sheath formed in a mesenchyme
What is the process of endochondral ossification?
- Primary ossification centre appears
- Chondrocytes hypertrophy and die:
- a) Thin layer of bone laid down under perichondrium -> Periosteum - Invasion of vascular cells surrounding periosteum break up cartilage
- Some cells differentiate into haematopoietic stem cells and make bone marrow
- Bone spicules are remodelled by osteoblasts and osteoclasts
Where does endochondral ossification occur?
In a pre-existing cartilage model
What do the somites on either side of the neural tube compartmentalise into?
Dermomytomes
Sclerotomes
What does the ventral sclerotome do to form what?
Forms a tube around notochord and segments into:
- Vertebral bodies
- IV discs
While the notochord eventually regresses, where does it remain and contribute to?
IV discs:
- Contributes to nucleus pulposus
What form of ossification forms the centra of vertebrae?
True endochondral
What is the ossification process of the neural arches?
Intramembranous followed by endochondral
What is the pattern of ossification of the centra? When?
One ossification centre
Bi-directionally from one area in lower thoracic/upper lumbar area - Around weeks 9-10
What is the pattern of ossification of the neural arches? When?
Two centres per arch From 2 areas: - Lower cervical/Upper thoracic - Lower thoracic/Upper lumbar - Around week 8
What are the references for the ossification of vertebrae?
Cunningham, 2017
Bagnall et al. 1977
Moore and Persaud, 2008
What are the PAX genes responsible for?
Segmentation of:
- Vertebral column
- Ribs
How many PAX genes are there in humans?
9
What did Smith and Tuan, (1994) find in regards to PAX genes?
Studied foetuses at 7-8 and 10-12 weeks
Found PAX1 only in the 7-8 weeks group
What did Peters, (1999) find in regards to PAX genes?
PAX1 and PAX9 have a synergistic effect:
- Both in different parts of vertebral column
- Double mutant mice had far more issues
What does the notochord signal the induction of? What happens if the notochord is removed? (Reference?)
Signals induction of PAX1
Removal -> Fused cartilaginous tube -> Klippel-Feil syndrome
(Fleming et al., 2001)
What is mechanobiology?
How a cell reacts to its environment by:
- Detecting external forces
- Measuring external forces
- Responding to external forces
What forces are involved in the mechanibiology of bone and what are these essential for?
The forces are mechanical loading
Essential in skeletal development
How do tissues (bone) respond to external forces (mechanical loading)?
Tissues will adapt their: - Function - Structure - Mass/Density In regards to bone - they change structure and density
What is a useful reference for mechanobiology?
Nowlan et al., 2010
What will an osteoprogenitor in the periosteum become and o if mechanical loading is:
- Present
- Absent
(Reference?)
Mechanical loading present = Osteoblasts -> Lay down new bone
Mechanical loading absent = Osteoclasts -> Reabsorption of bone
(Young et al., 2014)
In the cervical region, what initiates the neural arch ossification? (Reference?)
Gasp reflex
Bagnal et al., 1977
How does neural arch ossification initiate in the lumbar region? References?
Bagnal et al., (1977) - Limb muscle twitches
Land and Schoenau, (2008) - Due to kicking against resistance in womb
Why is there loss of bone mineral density after birth in the lumbar vertebrae?
There is kicking against no resistance
What did the Van der Meulen and Huiskes, (2000) study involve and show?
Tested mechanobiology in a group of rates
Constant strain on ulna -> Forced remodelling of bone:
- New bone created when compared to control
What are the two processes involved in skeletogenesis? (Reference?)
Histogenesis = Differentiation of cells
Morphogenesis = Formation of shape and size
(Eames et al., 2012)
What condition can result due to a large reduction/absence of foetal movements and hence abnormal skeletogenesis? How does it present?
Fetal Akinesia Deformation Sequence (FADS):
- Thin bones = Slender and hypomineralised (prone to fractures)
- Kyphoscoliosis
- Other spinal problems
- Joint contracture and talipes equiovarus
What is arthrogryposis?
Joint contractures in 2 or more places due to reduced foetal movements
What is developmental dysphasia of the hip?
Malformed hip joint:
- Partial/Full hip dislocation
What is the least common and what is the most common skeletal problem that can arise if Fetal movements are reduced?
Least common - Fetal akinesia deformation sequence
Most common - Developmental dysphasia of the hip
What did Frost, (2003) say regarding stress and strain and their effects on bone remodelling?
Strain had a greater effect on remodelling than stress
What group of people have a greater response to bone remodelling?
Young people
What do mechanical stimuli from muscle activity affect in regards to the skeleton?
Affect skeletal:
- Shape
- Size
Where is new bone usually added?
To areas under high stress
What cells achieve bone mass increases or adaptation due to mechanical stimuli?
Osteoblasts
Osteoclasts
Does physical activity need to be vigorous to result in bone remodelling?
No
Where is decreased bone mass and density seen?
In people who do little physical exercise
In patients under bed rest
In astronauts
What was the basis of the Rubin et al., (2002) study?
Testing to see if bone architecture changed with low levels of strain
18 sheep:
- 9 stood constrained and were oscillated for 20mins/day, 5 days/week
- These 9 sheep roamed free when not being oscillated with the other 9 sheep
What were the results of the Rubin et al., (2002) study?
34.2% increase in bone mineral density in the experimental group (p=0.01)
Showed that even low-intensity but regular stimuli stimulates bone formation
What conditions could result in absence of mechanical load and hence reduced bone growth?
Muscle absence
Paralysis
What is temporary brittle bone disease?
Bone fails to form in utero:
- Affects newborns
- Joint formation problems
- Due to reduced muscle movement
How does temporary brittle bone disease progress?
Mechanical stimuli after birth can return bones to normal in first few years
What does Shea et al., (2015) show in regards to muscle paralysis and skeletogenesis?
Joint and bone formation affected
Poorly defined bony features:
- Condyles
- Tuberosities
Nowlan et al., (2007) studied chick knees and paralysis. What were the results?
Joint A was unmoved: - Resulted in fusion of tibia and femur - Abnormal knee joint Joint B was moved: - Clearly developed joint
Will bone grow in muscle absence?
Yes
In muscle absence, what mice bones and joints were affected in the literature review by Nowlan et al., (2016)?
Vertebral column Ribs, sternum and manubrium Carpals and metacarpals Tarsals and metatarsals Scapulae Joints: - Elbow - Wrist - Ankle - Shoulder
In muscle absence, what mice bones and joints were unaffected in the literature review by Nowlan et al., (2016)?
Phalanges Clavicles Radius Joints: - Knee - Interphalangeal
In muscle absence, what mice bones and joints were areas of controversy in the literature review by Nowlan et al., (2016)?
Humerus Ulna Femur Tibia Hip joint
What are the other sequelae of muscle absence? (I.e. Apart from malformed bones and joints) (reference?)
Abnormal spinal curvatures Absent tuberosities Enlarged cervical vertebrae Partial fusing of cervical vertebrae (Lightfoot and German, 1998)
In what experimental model were all the other sequelae of muscle absence found? (Reference?)
All found in mice lacking striated muscle
Rot-Nikcevie et al., 2006
What effect do neuromuscular conditions have on bones?
Nerves controlling muscles affected -> Abnormal bone formation
What is the structure of bone in people with neuromuscular disorders?
Thinner and weaker
What are some examples of NMDs?
Spinal muscular atrophy
Duchenne’s muscular dystrophy
