Biomedical Engineering Reference
In-Depth Information
to baseline levels at 1 week. IGF-1 is high during the first four days, then
decreases at day 8 and increases later on. FGF-2 and BMp-2 peak at day 14,
then decrease. a strong correlation has been demonstrated between vEGF,
tGF-b and iGF-1, suggesting that they act coordinately in osteoprogenitor
cell growth. a similar correlation is evident among BMp-2, pdGF and
FGF-2, and between tGF-b and pdGF.
3.5.1 Bone morphogenetic proteins (BMP)
these belong to the tGF-b superfamily, which includes the BMp (except
BMp-1), tGF-b, growth differentiation factors (GdF), activins, inhibins and
the Müllerian substance. BMp are stored in the bone extracellular matrix and
are mainly produced by osteoprogenitor cells, osteoblasts and chondrocytes.
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other cell types can also synthesize BMp, such as endothelial cells, which
produce BMp-2.
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Mature osteoblasts and chondrocytes do not express
significant levels of BMP, but both have increased BMP expression in fracture
repair.
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BMp expression is induced by stimuli such as mechanical stress at
regions undergoing bone tissue formation.
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Even if BMp are structurally and functionally related, each type has a unique
role as well as a distinct temporal expression pattern during the bone repair
process.
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BMp-2 and -4 are expressed early by MSC, then are expressed
throughout the bone healing process. BMp-7 (also known as osteogenic
protein-1 or op-1) is expressed from day 7 and peaks at 2-4 weeks.
BMp induce a cascade of events for chondro-osteogenesis, including
chemotaxis, mesenchymal and osteoprogenitor cell proliferation and
differentiation, angiogenesis and synthesis of extracellular matrix. BMp-2
and -4 are chemoattractive proteins for mesenchymal progenitor cells
(MpC), suggesting a functional role for the recruitment of MpC during bone
development and remodelling, as well as in fracture healing. BMp-4 works
together with vEGF to recruit osteoblast precursors.
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BMp-2, -6 and -9
stimulate the differentiation of pluripotent MSC into osteoprogenitor cells
and BMp-2, -4, -7 and -9 further differentiate them to become osteoblasts.
BMp-2 upregulates runx-2 and osterix expression.
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BMp-2, -4, -6, -7
and -9 increase alkaline phosphatase and osteocalcin and lead to calcium
deposition.
Most BMp are able to differentiate osteoblasts into osteocytes. BMp-
13 stimulates the proliferation and differentiation of chondrocytes.
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BMp-14, also known as the growth differentiation factor-5, promotes the
chondrogenic differentiation and influences endochondral bone growth.
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BMp-2 through -7 and BMp-9 are able to induce
de novo
bone formation
after ectopic implantation.
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the osteoinductive activity of BMp-3 depends
on the experimental conditions and the stage of differentiation; it may have
an inhibitory effect in the presence of BMp-2 and BMp-7.
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BMp stimulate
