DDS Lecture 1- Bone (1) and Craniostynosis Flashcards
Endochondrial vs Intramembraneous Ossification
What are they and what bone types do they give rise to?
EO- bone production in which mesenchyme
undergoes transformation into cartilage, with cartilage then replaced by bone. This type of bone is best represented by the long bones of the body
IO- bone arising from mesenchyme.
This type of bone composes most of the craniofacial complex and some of the clavicle.
4 cell types of endochonrial ossification
- chrondrocytes: derrived from paraxial mesoderm, lateral plate mesoderm and neural crest cells
- osteoblasts: mesenchymal stem cells
- osteocytes: osteoblasts trapped in bone
- osteoclasts: macrophage progenitor cell
Epiphysis vs Diaphysis
E- top of bone; resting chondrocytes; where bone elongates
D- growth plate; 2nd portion contains prehypertrophic chondrocytes (not proliferating much)/ undergo hypertrophy
What genes regulates following cycles:
1) proliferation
2) prehypertrophic
3) hypertrophic
1) FGFR3; BMP; SMO
2) FGFR3; PPR
3) BMP
REVIEW SLIDE 6!!
Blomstrand chondrodysplasia
Loss of function mutation in PTHrP leading
to accelerated bone formation and early
death.
you loose PPR block on PH, so not enough precursor cells will be made.
What’s the function of the Bmp pathway?
promotes chondrogenesis (proliferation)
What’s the function of the FGFR pathway?
The net effect of this signaling loop is to regulate chondrocyte differentiation (inhibit proliferation/ prehypertrophic stage)
T/F: blocking Fgfr 3 wouldLead to increased maturation of proliferating chondrocytes to prehypertrophic chondorcytes.
True!
Achondroplasia (ACH) (5)
Fgfr3
- Reduced growth of the long bones (proximal structures more severely affected than distal structures).
- Frontal bossing of the cranium
- Cranio-somatic disproportion
- Compression of the foreamen magnum
Achondroplasia-
Why disproption between bones in legs/ arms to head?-
facial head form from membraneous ossification, not through cartilage (doesn’t go through same signaling process)
______ activates STAT pathway, which induces cell cycle inhibitors.
FGFR3
Overactivation of FGFR leads to overactivation of cell cycling?
What are 3 STEPS in intramembraneous ossification?
mesenchymal cell –> Osteoprogenitor Cell –> osteoblasts –> osteocytes
- osteoblast get trapped and turn into osteocytes
- OC undergo mitotic division and differentiate into an osteoblast
What are the genes involved in intramembrraneous ossification regulation? (8)…. Which one is the main molecule to regulation IO?
Twist1/ Hand2, Runx2/ Osx, Hoxa2, SATB, ATF4
Runx2 is the main regulator
Celidocranial dysplasia
inactivation of Runx2
- clavicular hypoplasia
- large open sutures in the skull
- wide pubic smphysis
- dental abnormalities (missing or supernumerary teeth
T/F: Without Runx2, you’ll get full maturation of the bone.
False;
w/O Runx2, you don’t get full maturation of bone
ex- cleidocranial dysplasia
bones (facial bones and the frontal bone of the skull) develop from what? (2)
neural crest cell-derived or unsegmented paraxial (head) mesoderm-derived mesenchyme.
Most craniofacial skeleton is derived from what type of ossification?
Intramembraneous Ossification
What are 3 types of joints in the body?
fibrous, primary/ secondary cartilaginous and synovial
Fibrous Joint
These joints have no joint cavity and are connected via fibrous connective tissue.
Cartilaginous Joint (3)
- are connected entirely by cartilage (fibrocartilage or hyaline).
- allow more movement between bones than a fibrous joint but less than the highly mobile synovial joint
- Two types: primary/ secondary CJ
Synovial Joint (3)
- filled with synovial fluid
- allows significant movement
- ligaments are associated with SJ’s to provide strength
What are 2 types of cartilaginous joints? describe them
- Primary cartilaginous joints; bone and cartilage are in direct apposition to each other (costochondral joint)
- Secondary cartilaginous joints; bone-cartilage-fibrous tissue-cartilage-bone (pubic symphysis)
What are 3 types of fibrous joints? describe them
- The suture (cranial); no joint movement (synarthrosis)
- The gomphosis (tooth socket); the tooth is attached to the underlying bone by the fibrous periodontal ligament. Limited movement is allowed (such as during biting or orthodontics)
- The syndesmosis (radius/ulna and tibia/fibula); bones are some distance apart and connected by an interosseous ligament that permits limited movement- helps avoid injury
_____ are articulations or growth sites that allow adjacent bones to expand while maintaining
orientation at their junctions. Connective tissue in the suture, called ______, contain osteogenic cells which provide for new bone growth.
Sutures; syndesmosis
What are 4 types of skull sutures involved in craniosynotosis? Where are they located?
- Metopic suture
- Coronal suture
- Sagital suture- longest
- Lamboid suture
NOTE: Types of sutures forms is dictated by the stress it received during development.
syndesmosis
an immovable joint in which bones are joined by connective tissue (e.g., between the fibula and tibia at the ankle)
What are 3 types of syndesmosis sutures?
- simple suture
- serrated (interdigitating) suture
- squamosal suture
Simple Suture (2)
- contains CT and blood vessels that separate oppsing bony fronts
- osteoblasts w/in bony fronts form bone to provide growth for this suture
Serrated (interdigitating) suture
- Interdigitating extension of bone from both adjacent surfaces form a strong suture
- Connective tissue still persists between the bony fronts.
- Coronal sutures are serrated.
Squamous Suture (2)
- These are overlapping sutures, with connective tissue and blood vessels appearing between the bony fronts.
- One example of a squamous suture is the suture between the parietal and temporal bones.
Coronal suture is what type of suture? The suture between the parietal and temporal bones is what?
Coronal- serrated/ interdigitating suture
p/t- squamous suture
A second suture type exisists along the facial midline, with articulations along the midline with interposing bands of cartilage. What type of articulation is this?
Synchondrosis
Craniosynostosis
- joints between the bones of an infant’s skull close prematurely, before the brain is fully formed
- 20% are syndromic (occurs w/ other defects in body)
- associated w/ brain abnormality
- surgery: separate fused bone
Types of Craniosynostoses:
1) _______: fusion of coronal/ lambdoidal
2) ______: fusion of metopic suture
3) ______: fusion of sagital suture
4) ______: fusion of coronal suture
1) Plagiocephaly
2) Trigonocephaly
3) Scaphocephaly
4) Oxycephaly
What’s the goal of treatment of craniosynostoses?
reduce the prssure in the head and correct deformities of the face/ skull bones (early treatment while bones still soft)
Explain how FGF causes craniostynosis…
- The closer you are to FGF signal, there’s an increase of differentation/ bone development.
- The further away, the more proliferation…
-Too much differentiation= craniostynosis
NOTE: SEE SLIDE 55
