Orthomech L1: Skeletal development

  1. What are the 5 Steps to joint development?
    • Have the cartilagnious template in the womb
    • Mesenchymal condensation
    • Joint formation
    • Interzone formation: Not dependent on mechanical environment
    • Morphogenesis: Prenatal movements important to dertermining joint shape
    • Joint maturation: Cavitation occurs (physical separation of rudiments). Mechanical forces important here. Possibly joint movement causes small tears to form in the structurally weak interzone?
  2. What aspects of joint development are affected by joint movement? How do we know this?
    • Joint shape: Prenatal movements are crucial
    • Cavitation?
    • Joint separation? Joint movement causes small tears to form in the structurally weak interzone

    In muscleless mice the joint shape is poorly defined and not separated. But the interzone still forms which implies that muscle movement only defines joint shape.
  3. What is cavitation? How does it happen?
    Separation of rudiments.

    Current theory is that small tears in structurally weak interzone form and propogate due to limb movement.
  4. What is the interzone? What is its function?
    A trilaminar structure with two outer layers of cartilage separated by a layer of flattened collagen I producing mesenchymal cells.

    Its function is to divide the cartilaginous templates
  5. Is the typical columnar arrangement of articular cartilage seen in prenatal development?
    No, but cells that become articular cartilage have certain genetic markers
  6. How does adult articular cartilage get its columnar arrangment?
    not known
  7. What are the two types of ossification that occur during development?
    Intramembranous ossification: (When MSCs differentiate directly to bone.) MSCs form an aggregate and differentiate into osteoblasts which secrete osteoid matrix

    • Endochondral ossification:
    • mineralisation of pre-existing cartilage to become bone tissue.
    • 1. Cartilage is replaced by mineralised tissue
    • 2. The chondrocytes become hypertrophic and secrete enzymes for mineral deposition
    • 3. Matrix calcifies  
    • 4. chondrocytes undergo apoptosis
    • 5. Blood vessels invade, brining in osteoprogenitor and haematopeitic cells
    • 6. Osteoblasts use the calcified matrix as a scaffold and secrete osteoid to form bone.
  8. Give examples of structures that intramembranous and endochondral ossification form.
    • Intramembranous: Dermal and perichondral bone
    • Endochondral: Fuure cancellous bone, most of vertebral column, sternum and sesamoids
  9. What is a primary and secondary of ossification?  Where is primary and secondary for long bones?
    • Where ossification first occurs. Secondary centre is where ossification occurs after primary centre has appeared.
    • For long bones, primary is diaphysis, secondary is epuphysis
  10. Outline the stages for long bone development
    • 1. Bone collar forms around cartilaginous template
    • 2. Cavitation of the long bone occurs
    • 3. Periosteum bud invades bringning in osteoprogentors and haematopoeitic cells
    • 4. Medullary cavity forms
    • 5. Secondary ossification site appears in preparation for stage 6
    • 6. Ossification of epiphysis occurs once completed hyaline cartilage remains only in the epiphyseal plates and articular cartilages.
  11. What is a growth plate
    The epiphyseal plate(or growth plate) is a hyaline cartilage plate in the metaphysis at each end of a long bone. It is the part of a long bone where new bone growth takes place
  12. What is growth due to prenatally and post-natally?
    • Prenatally: Longitudinal growth of diaphyseal growth plate
    • Post natally: Growth at epiphyseal and diaphyseal growth plate
  13. What the heck is skeletal maturity?
    When growth stops when the diaphyseal and epiphyseal centres of ossification meet.
  14. What is achondroplasia, what is it caused by?
    • It is caused by a mutation in the FGFR3 gene which limits the progress of ossification
    • Common cause of dwarfims
  15. What is rickets, what is it caused by?
    A disease caused by vitamin D deficiency resulting i weakened bones etc
  16. What is developmental hip dysplasia, and what is is caused by
    • Hip joint is dislocated
    • Can be caused by genetic factors, too tight swaddling, breech presentation, lack of in utero fluid. 
    • More likely in females
  17. What is athrogryoposis and what is it caused by
    Multiple joint contracture. Many genetic causes with end result being restricted movement in the womb
  18. What was the hypothesis and conclusion of the muscleless mice experiment?
    Embryonic muscle contractions are ciritcal to normal development of normal tissues and structures in embryonic mice.

    Conclusion: Hypothesis partially corroborated. Ie some skeletal structures are dependend ton embryonic muscle contractions. 

    • Could be due to biochemical factors : Some regions more sensitive to the lack of diffusable factors
    • or biomechanical factors: different levels of mechanical forces could exist in diffferent regions of skeleton in normal or mutant embryo
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Orthomech L1: Skeletal development
Skeletal dev