JCII: Modeling of Phosphate Ion Transfer to the
Surface of Osteoblasts under Normal Gravity and
Simulated Microgravity Conditions.
Lindsay Crowl
Feb. 1, 2006
Prolonged exposure of astronauts to microgravity leads to major bone
loss, most of which occurs in weight-bearing bones such as the femur. For
this reason, bone loss is thought to be due to an increase in bone resorption
and/or a decrease in bone formation. This change in bone cell metabolism
is thought to be caused by the lack of mechanical stimulus (stress and/or
strain) due to low gravity conditions.
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1 Background/Review
The Players:
Osteoclasts- Bone destroyers. \Huge" multi-nucleated cells that cause
bone resorption by secreting acids and enzymes that break down the
bone matrix. They release calcium into the blood stream and hence
can help regulate calcium levels in the body. Osteoclasts are mobile
cells that are often found in cavities of old bone. The average life-span
of an osteoclast is about 12 days and they vary in size from 20-100
microns in diameter.
Osteoblasts- Bone (re)builders. Osteoblasts synthesize osteiod, which
then minerlizes to form the bony matrix. They arise from marrow
stroma cells and eventually turn into osteocytes, bone lining cells, or die
by apoptosis. The life-span of an osteoblast varies from a few to about
100 days, and are typically about 10 microns in diameter. They secrete
alkaline phosphatase during bone formation. this removes phosphate
groups from proteins, and hence increases the Pi concentration.
Osteocytes- Most numerous type of bone cell, and look like spiders
with about 50 nger-like processes that run through canaliculi. They
live in the lacuna and facilitate the exchange of nutrients in bone. It is
also currently assumed that they serve some sort of mechno-tranduction
purpose and can send signals to other bone cells to stimulate the remodeling of bone in need of repair. They originate from retired osteoblasts.
Bone Lining Cells- Live on the outside of bone, cover bone surface.
Also retired (inactive) osteoblasts.
Possibilities for Bone Loss:
Osteoblasts don't get recruited to BMU site, and therefore cannot rebuild the bony matrix.
Osteoblasts become prematurely apoptotic. i.e. they can't nish their
job.
Osteoclasts get recruited more often than normal, or to places that
aren't in need of remodeling, since there is no perfered orientation in a
low gravity environment.
Osteoclasts fail to become apoptotic after remodeling is over. i.e. they
become pyscho-killers.
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2 What is a BMU?
The basic multicellular unit (BMU) is a group of bone cells that remodel
osteons in cortical and cancellous bone. Remodeling renews existing bone
in a sequence of resorption (osteoclasts) and formation (osteoblasts). It can
take about 3 months to rebuild an osteon, which is much longer than cells
that make up the BMU live.
When the team of osteoclasts break down the bony matrix, calcium and
phosphate ions are released into the surrounding bone uid, since mineralized
bone's major component is hydroxyapatite, Ca3 (PO3)2 . Phosphorous ions
can be a powerful apoptogen, and have been shown to initiate apoptosis in
osteoblasts.
What is the fate of the osteoblasts once they form new bone? Lucky ones
will retire and become osteocytes. A select few become bone lining cells. The
rest, well they \undergo apoptosis." RIP osteoblasts. I will miss you when
I'm 50+.
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3 Model Hypothesis:
Does microgravity modulate normal osteoblast developement and induce cell
death? Biological experiments show that this is a very reasonable assumption. This paper presents a numerical model in which the local phosphate
ion concentration increases in a microgravity environment, and this in turn
causes increased (and/or premature) apoptosis in osteoblasts.
4 Species Transfer Model:
The goal of the model is to analyze the Pi concentration on the surface of
osetoblasts for two dierent straining ows: (1) normal gravity, (2) simulated
microgravity (low shear stress).
The model tracks phophorous ion concentration on a 2D spactial domain
in which osteoclasts are resoding bone next to a group of osteoblasts. Shapiro
et. al. treat osteoclasts as Pi sources, and osteoblasts as Pi sinks (I include
this fact so Molly can relate this model to her bunnies in a eld model :)
Conside the geometry of the model. Is it oversimplied? Trabecular bone
is not where bone loss occurs in low gravity conditions. The entire basis of
this model is based on shear stress for ows in the lateral direction.
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