Hello, my name is Michaela Kneissel.
And I'm based at the
for BioMedical Research
I'm going to talk today
about some of the pathways
which control bone formation.
I will start off with a brief
introduction to bone homeostasis
before speaking about three pathways
which regulate bone formation.
I choose to highlight those out
of the range of relevant pathways,
as they are the major pathways
targeted to date for the treatment
of bone diseases and injuries.
First and foremost, I will
introduce you to Wnt signaling,
its crucial role in
bone formation, and how
the pathway is currently targeted
for the treatment of bone fragility.
In particular, I will spend some
time explaining the role and
mode of action of the Wnt
which is a key negative
regulator of bone formation.
I will then also introduce briefly
the impact of parathyroid hormone,
or PTH signaling on
bone formation, and how
it is used to treat osteoporosis.
Finally, I will touch on
the importance of bone
or BMP signaling,
and how its modulation can be
used to promote bone healing
or hinder excessive formation.
And I will highlight some
of the cross-talk that exists
between these three
pathways and the regulation
of bone homeostasis.
The skeleton contains three major
cell types-- osteoblasts and the
derived osteocytes and osteoclasts.
Osteoblasts form bone.
Osteoclasts resorb bone.
And osteocytes maintain bone and
contribute to the regulation of
osteoblast and osteoclast activity.
Bone forming osteoblasts arise from
pluripotent mesenchymal stem cells.
Wnts, PTH, and BMPs are
amongst the key factors
that enable mesenchymal
stem cell differentiation
towards the osteoblast lineage.
together with chondrocytes
from a common
precursors undergo proliferation,
followed by differentiation into osteoblasts.
Osteoblast differentiation requires
activation of the key transcription
factor Runx2, also termed Cbfa1.
which then mineralizes end materials.
At the end of the bone
matrix forming activity,
osteoblasts either undergo apoptosis
or become dormant lining cells
on the bone surface or turn into
The latter represent over
90% of all bone cells,
and are interconnected with each
other in cells on the bone surface
by an extensive canalicular
network in which the osteocyte
dendritic processes are contained.
also exists between cells
of the osteoblastic
lineage and osteoclasts
which are of hematopoietic origin.