limbs and back week 5 Flashcards
How are long bones, vertebrae pelvis and bones of the base of the skull formed?
They are preceded by the formation of a continuously growing cartilage model which is progressively replaced by bone. This process is called endochondral ossification.
What is the benefit of endochondral ossification?
It permits functional stress to be sustained during skeletal growth
Describe the growth of the hyaline cartilage template for long bones
a small model of the long bone is first formed in solid hyaline cartilage.
This undergoes mainly appositional growth to form an elongated dumbbell shaped mass of cartilage of a shaft (diaphyses) and future articular portions (epiphyses), surrounded by perichondrium
Describe the process of bone formation
Ossification starts when proliferated chondrocytes deposit an extracellular matrix containing type II collagen
The chondrocytes in the central region of cartilage undergo hypertrophy and synthesise type X collagen - a marker for hypertrophic chondrocytes
Angiogenic factors are secreted by hypertrophic chondrocytes (VEGF) which induce the invasion of blood vessels from the perichondrium to form a nascent bone cavity
As the cartilage matrix becomes calcified the chondrocytes degenerate leaving spaces for blood vessels to invade
Osteoprogenitor cells and haematopoietic stem cells reach the core of the calcified cartilage through the perivascular connective tissue.
The preosteoblasts differentiate into osteoblasts and aggregate on the surfaces of the calcified cartilage and begin to deposit bone matrix
What is indian hedgehog?
a member of the hedgehog proteins, is expressed by early hypertrophic chondrocytes within the endochondral template
What are the functions of Ihh?
Stimulates adjacent perichondria chondrocytes to express RUNX2 and differentiate into osteoblasts to continue the bone collar
Stimulates the perichondral cells to produce parathyroid hormone related peptide (PTHrP)
What does PTHrP do?
binds to receptor on surface of chondrocytes of the reserve zone to stimulate their proliferation
Binds to receptors of chondrocytes in the proliferation zone to inhibit their differentiation into hypertrophic chondrocytes
What causes growth plate inactivation?
An increase in oestrogen secretion
What causes achondroplasia?
Heterozygous mutations of fibroblast growth factor 3 receptor. FGF3 mutations activate the FGFR3 signal pathways which is a receptor tyrosine kinase pathway. The ultimate effect of FGFR3 signalling on bone growth is inhibitory.
What is the phenotype of achondroplasia?
long trunk, short limbs, especially proximally and a large head.
What is the mutation observed in achondroplasia?
gain of function mutation which activates the receptor
How do somites contribute to muscles?
musculature of the axial skeleton, body wall, limbs
somites undergo epithelialisation
upper region - dermatome, dorsomedial muscle cells, ventrolateral muscles cells
lower region - vertebrae and ribs
What directs dermatome to form dermis?
neurotrophic 3
What do WNT proteins and MBP proteins do?
WNT (activation), BMP (inhibitory) combine to activate MYOD- creating a group of muscle precursors that secrete MYF
What do MYOD/MYF5 do?
myogenic regulatory factors - activate muscle specific genes, can convert non muscle cells to muscle cells
What induces sclerotome formation?
sonic hedgehog and noggin
Describe the lateral somatic frontier
well defined border between each somite and the lateral plate mesoderm
Separates primaxial and abaxial domain
LSF also defines border between dermis derived form dermatome, and the dermis derived from the lateral plate mesoderm in the body wall
What signals control primaxial?
neural tube and notocord
What signals control abaxial?
lateral plate mesoderm
