Molecular Aspects of Temporomandibular Joint Development

• What is the TMJ?

  The temporomandibular joint is a hinge & gliding joint & is the most constantly used joint in the body
• What does the TMJ look like when the jaw is opened and closed?

  closed- disc is sitting nicely sandwiched between the condyle and fossa

  opened- disc moves forwards and gets squeezed.

  
• What is meant by the term TMJ disorders?

  Dysregulation of the TMJ, muscles & disc
• How might TMJ disorders arise?

  - Mineralisation of the disc in old age

  - Poor natural repair of of the disc & condylar
• What does the TMJ consist of?

  - It forms between the mandibular or glenoid fossa of the temporal bone & the condylar process of the dentary mandible

  - A fibrocartilage disc forms between these 2 skeletal elements, surrounded by synovial fluid in a capsule

  
• what is the name of the articulation site into which the mandibular condylar inserts?

  mandibular or glenoid fossa
• What does the temporal bone comprise?

  The temporal bone is a composite bone which comprises the petromastoid, squamosal, tympanic & styloid

  
  

  - squamosal creates the socket in the temporal bone

  
• What is the proximal part of the human mandible (dentary) divided into?

  3 processes:

  Coronoid process

  Condylar process

  Angle

  
• Where does the articulation with the temporal bone occur?

  At the condyle, while the angle & coronoid act as muscle attachment sites

  
• show the ligaments of the TMJ

  
• What stops the jaw from dislocating?

  - Sphenomandibular ligament

  - Stylomandibular ligament
• Is the TMJ unique to mammals?

  yes
• Describe the difference in jawed joints between mammals and non-mammals.

  - All non-mammalian jawed vertebrates use a jaw joint formed between 2 cartilaginous bones, the quadrate & articular

  (dentary and squamosal bone are far and do not come into contact)

  
  

  - In mammals, these bones have been incorporated into the middle ear and are homologous to the incus & malleus

  (dentary and squamosal bone are close)

  
• What are some congenital (a condition or trait that exists at birth) defects associated with the TMJ?

  - Ankylosis (fusion) of TMJ

  - Auriculo-condylar syndrome- characterised by TMJ defects (100%) and condylar defects (75%)

  - Under & overgrowth of condylar- leading to defects in jaw size
• How is a jaw articulation made?

  - Patterning of the dentary

  (intramembranous ossification- without cartilage template being made first (we go straight to bone))

  
  

  - Capping of the bone with secondary cartilage

  
  

  - Formation of a disc

  
  

  - Transformation of the cartilage into bone

  (endochondral ossification)
• explain the differences in the dentary of different mammals

  - one bone makes whole of lower jaw

  - all have condylar (jaw articulation site)

  - there are differences in the coronoids depending on the animal

  - there are differences in the angle process size

  
• Describe the TMJ of a mouse.

  - has a main condylar process which acts as the point of articulation with the squamosal

  - Anterior to this is found the coronoid process & posterior is the prominent angular process

  
• How can you tell an animal has a big bite force from the dentary bone?

  if the coronoid process is large (lots of muscles attach to it and are associated with the jaw closing muscle)
• What is different about the TMJ in a TGF-beta2 knockout mouse?

  Loss of angular

  
  

  (because TGF-beta2 forms the tendon and muscle attachment on the angular process)

  
• Why is there a loss of angular in the TMJ of a TGF-beta2 knockout mouse?

  - The 3 process pattern is initially normal in the mutant

  - Loss of TGF-beta2 leads to loss of muscle attachment due to a defect in tendon formation

  - Loss of the angular leads to a loss of mechanical stimulation
• What is different about the TMJ in a Pax9 mutant mouse?

  Loss of the coronoid

  
  

  (because expression of Pax9 is restricted to the developing coronoid)

  
• Is there still muscle attachment even if there is no coronoid process in a Pax9 mutant mouse?

  yes

  
• Are the 3 processes at the back of the dentary under separate genetic control?

  Yes
• since the 3 processes at the back of the dentary are under separate genetic control,

  What does this allow?

  A greater flexibility & ability to cope with changing diets & lifestyle
• What can defects in the patterning of the dentary be caused by?

  Mechanical factors or intrinsic defects in the forming bone
• Compare secondary cartilage in mice and humans.

  • In both mouse and human secondary cartilage forms at the condyle.

  In humans this is largely replaced by bone half way through gestation, except at the articulation site which remains cartilaginous for much of adult life.

  
  

  • In humans secondary cartilage also forms along the anterior coronoid border, but disappears before birth.

  
  

  • In the mouse secondary cartilage is associated with the prominent angular (acts as growth center to increase size of angular process)
• How can you change the shape of the dentary during development?

  - attach muscles that pull on developing bone structures to enhance bone growth

  - add secondary cartilages and form larger surface areas for muscles to bind to and increase the size.
• Where does the disc form?

  On top of the condylar cartilage

  
  

  - the synovial cavities cause the disc to lift off the condyle.

  
• how is the disc removed from the condylar?

  High levels of lubricin are expressed are form the synovial fluid in the synovial cavities which act to separate the disc from the condylar.

  
• Why are muscles important for disc formation?

  Allows fetal jaw movement (mechanical stimulation)

  
  

  -> in the absence of muscle action, the disc doesn't lift off the condylar.
• Diagrammatically show the process of human TMJ development.

  - disc progenitor cells form

  - 2 synovial cavities form (lifting the disc from the condyle)

  
• what mammals do not have a disc in the TMJ?

  mammals without teeth (anteater, baleen whales, platypus etc)

  
  

  -> the disc starts to form but does elevate off the condyle.
• what is Indian hedgehog gene important for?

  bone and condylar cartilage and disc
• what happens if there is a loss of Indian hedgehog gene?

  leads to reduction in condylar cartilage and a failure in disc formation

  
  

  - gene that responds to mechanical stimulation (when cell is pulled and stretched, the gene is turned on).
• what does a defect in the formation of the disc lead to?

  a fusion of the joint (ankylosis)
• What do condylar defects affect?


  The developing glenoid fossa

  
• What does the secondary cartilage act as?

  A growth centre extending the bony processes of the dentary

  
  

  - Within the condyle chondrocytes pass through proliferative and hypertrophic zones before being replaced by osteoblasts and bone matrix.
• What are the different layers in the condylar?

  In the outer regions the chondrocytes are flattened, towards the centre rounded. As they move inferiorly they become hypertrophic.

  -> the hypertrophic cells go through endochondral ossification and formation of bone

  
  

  (Most of the proliferation is in the progenitor cells in the polymorphic cell layer beneath the articular layer)

  
• Why is it important to have a balance of differentiation & proliferation?

  - Too high proliferation leads to more growth and enlarged condyles

  - Too high differentiation depletes the pool of progenitor cells & leads to shortened elements: achondroplasia

  
  

  • Balance is disrupted in a number of human disorders, such as thanatophoric dysplasia and can also lead to asymetrical overgrowth of the condylar
• What does endochondral ossification in the condylar rely on?

  Mechanical stress, otherwise it might be reduced or fail completely