L12 : Skeleton Flashcards
where does skeleton of the body axis originate?
sclerotome only
what tf contribute to sclerotome
pax 9 and pax1
where does the limb skel originate
lateral plate mesoderm
what are teh three origins of the overall skeleton
sclerotome
somite
lpm
how do the first skeletal strucutres form
through pre-cartilage condensation
what is important about ecm in the early skeletal mesenchym
contains lots of hyaluronan
a glycosaminoglycan which serves as a cell spacer
what are the mechanisms of pre cartilage condensation
change in ECM
expression of enz that removes hyaluronan
alternative splicing of fibronectin - exon EIIIA only
present in condensing state only
expr of N-CAM nd N-cadherin
occurence of gap junctions
how doe migrating precursor cell turn into skeltal tissue
pre cartilage condensation
how is the skeletal tissue subdivided into specific bones
Hox gene role in limb patterning
in joint - imbetween hox/signal pathways/ muscle contraction
what signalling pathways do joints require
Wnt/BMP/GDF5/Ihh/integrins
what instigates the chnage from joint progenitor cell to commited joint cell
muscle contraction
shown by KO
what is the process through which bones elongate in dev
endochonral ossification
what is endochondral ossification
cartilage tunring into bone
range of differentiation steps
how is cartilage made
cartilogeneiss
mesenchyme condensation
what are some of the transitions in differentiation steps
chondroblasts in resting zone
columanr chondrocytes (prolif)
pre-hypertrophic chondrocytes (transition state not prolif)
hypertrophic transition start secretig ECM and increase in vol therfore become mineralised and sttract blood vessels
chondrocyte prolif and matix secretion = bone growth
what is the role of osteoblasts
accompany vascular invasion
become bone collar
cell which secrete the substance of bone
what happens at puberty
growth plate disappears (epiphyseal fusion)
where is the proliferation capacity ?
in resting zone cells
if transplant show young have the incr growth
what are some systemic factors involved in senescence
igf
thyroid (hypo = low growth)
estrogen (castration before pub incr bone growth)
what are the three principles of signal for bone growth
ECM
TF
long range signals
when are diff collagen expr
early chondroblast and columnar chondroblast - col2a1
pre-hyp chondrocyte - hypertrophic chondorcyte - col10a1
osteoblasts expr col1a1
what the ptype of mut col2a1
kniest disease
and types of dysplasia
mut affect chondrocyte survival /decr bone growth
what the ptype of mut col10a1
ko viable and normal
but dom mut have metaphyseal chondrodysplasia type schmid
autosomal dom mut collagen X - shortened stature /growth plates abn
what is the role of SOX9
master reg of chondrogenesis
dbl mut - no expr of chondrocyte specific markers
req for all aspects of limb dev
how does sox9 act col2a1
direct
and indirect sox5/6
what the role of sox5/6
act col2a1
ko display severe generalised chondrodysplasia
what is the role of BMP in chondroblasts
is a potent inducer of chondorgenic and osterogenic fates
support prolif of chondorcyte in growth cartilage induce expr ihh
what is the role of Runx2
promotes chondrocyte differentiation
promotes eo
ko loss of bone size
how is runx2 regulated
act ihh promoter inh by PTHrP role in neg feedback induces expr Vegf in hypertrophic chondrocyte and induce expr of Vegf-r in bone collar
what is the role of Vegf
vegf attract endo cells
- vascularisation
what is the interlink between osteoblasts and vasculature
accompany endo cells and depend on Vegf signals
what is the role of MMP-9
expr chondroclast - help degrade cartilage ECM
what long range signals involved in bone growth
ihh-PTHrP loop
wnt
describe the ihh-PTHrP loop
PTHrP = ligand expr at early chondroblast
rec expr in chondro and hypertrophic chond
(promote ch prolif and inh Runx2 at cert distance)
runx2 act ihh
fgf inh ihh
ihh upreg PTHrP
ihh = ligand expr pre-hyper ch
rec expr chondroblasts/cytes/ osteoblasts
keeps disticnt signal areas
