Achondroplasia and endochondral bone growth Flashcards
Explain, in detail, the process of endochondral bone growth
stages: development of cartilage model - primary ossification centre
Development of cartilage model: mesenchymal stem cells aggregate in the general shape of the future bone and develop into chondroblasts. The chondroblasts secrete the cartilage ECM, producing a cartilage model consisting of hyaline cartilage.
Growth of cartilage model:
Once the chondroblasts have been surrounded by cartage matrix they become chondrocytes. Chondrocytes divide and continue to secrete cartilage matrix so that the cartilage model grows.
Development of primary pacification centres:
Chondrocytes enlarge and resorb the cartilage to form trabeculae of cartilaginous matrix. The cartilage matrix becomes calcified and as nutrients can no longer reach them, the chondrocytes die.
At the same time, a nutrient artery penetrates the perichondrium towards the centre of the cartilage model. Blood vessels and osteogenic cells invade the spaces left behind by the dead chondrocytes. Osteogenic cells develop into osteoblasts and form spongy bone.
As the perichondrium becomes reloaded by bone it forms the periosteum. As most of the cartage gets replaced by Bone, a primary ossification centre develops in the middle of the cartilage model. POC develops from the centre and spreads towards Both ends of the long bone.
Explain, in detail, the process of endochondral bone growth
stages: development of medullary cavity - epiphyseal growth plate
Development of medullary cavity: as the POC reaches the ends of the bone, osteoclasts break down the newly formed spongy trabecular bone. This creates a medullary cavity in the diaphysis.
Development of the secondary ossification centre: when the developing arteries reach the epiphysis, the secondary ossification centres develop, usually at the time of birth. Here, the spongey bone that is formed, remains. Compared to POC, the SOC grows outwards.
Formation of articular cartilage and epiphyseal growth plate:
The hyaline cartilage that covers the epiphysis becomes the articular cartilage. Hyaline cartilage remains between the epiphysis and diaphysis and is known as the epiphyseal growth plate.
What are the zones of the epiphyseal growth plate?
Resting zone Proliferation zone Hypertrophic zone Calcification zone Ossification zone
What type of growth does epiphyseal growth plate provide?
Growth in length of bone
Describe what is found in resting and proliferation zone?
Resting zone: Small, inactive chondrocytes are arranged in clusters
Proliferation zone: chondrocytes undergo cell division
Describe what happens in hypertrophic, calcification and ossification zone?
Hypertrophic zone: chondrocytes enlarge and signal the surrounding matrix to calcify
Calcification zone: matrix becomes calcified and chondrocytes die, having behind trabecular shaped cartilage.
Ossification zone: osteoclasts digest the calcifies cartilage and osteoblasts replace the cartilage with bone
What are the four basic categories of chemical signaling?
Autocrine
Paracrine
Endocrine
Direct contact dependant
Describe the origin of signals in paracrine signalling and how it acts?
Paracrine signal: Chemical messengers are released
Act locally
what is achondroplasia
a genetic disorder which causes the shortening of limbs. It is the most common form of short limb dwarfism
List the characteristic features of achondroplasia
Macrocephaly (abnormally large head) Frontal bossing: prominent, protruding forehead Midface hypoplasia (small midface) Sunken nasal bridge Protruding jaw Excessive skin folds Disproportionate length of limbs Small chest Joint laxity (loose ligaments) Spinal deformity
What is the mode of inheritance of achondroplasia
Autosomal dominant
Describe the pathophysiology of achondroplasia
A point mutation (substiution) occurs, swapping glycine to arginine on chromosome 4 of Fibroblast Growth Factor Receptor 3 (FGFR3). This makes the receptor continually active, resulting in:
Inhibiton of chondrocyte proliferation in growth plate
Reduced cartilage matrix production
Decreased endochondral ossification
What is the normal role of FGFR3
FGFR 3 is a negative regulator of endochondral ossification and inhibits proliferation and differentiation of the growth plate chondrocytes.
