Biomedical Engineering Reference
In-Depth Information
osteochondroprogenitor cells. osx may be induced by additional signalling
pathways acting in parallel to, or independent of, runx2. it has been shown
that Runx2 is required but not sufficient for the BMP2-mediated Osx induction,
since MapK and protein kinase d (pKd) signalling pathways serve as points
of convergence mediating the BMp2 effect on osx expression in MSC,
as well as other transcription factors downstream of BMp2. Cooperation
between NFat and osx activates the Col1a1 and osteocalcin promoters
and accelerates osteoblast differentiation and bone formation in a runx2-
independent manner.
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3.5 Role of growth factors in bone repair and
regeneration
Growth factors (GF) are polypeptides that act locally as modulators of cellular
functions. Their action may be autocrine (GF influences the cell of its origin
or a cell with the same phenotype), paracrine (GF influences a neighbouring
cell with a different phenotype) or endocrine (GF acts on a cell located at
a remote anatomical site).
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a single GF may have effects on multiple cell
types and may induce different functions. GF bind to target cell receptors
and induce an intracellular signal transduction that reaches the nucleus and
determines the biological response. this system is redundant, a single GF
may bind to different receptors.
the most important GF acting on bone are bone morphogenetic proteins
(BMp), transforming growth factor-b (tGF-b), fibroblast growth factor (FGF),
platelet-derived growth factor (pdGF), vascular endothelial growth factor
(vEGF) and insulin-like growth factors (iGFs) (table 3.4). as previously
mentioned, during bone repair and regeneration, GF are produced by the
cells of the microenvironment, such as inflammatory cells, fibroblasts,
endothelial cells, BMSC and osteoblasts. GF play a role during all the phases
of bone repair. In the inflammation phase, the major contributors are the GF
released by platelet a-granules (tGF-b, pdGF, vEGF and iGF), whereas
macrophages and other inflammatory cells secrete FGF, PDGF and TGF-b.
Migration of osteoprogenitors is enhanced by BMp, pdGF, FGF and vEGF.
pdGF and FGF also stimulate the proliferation of periosteum-derived cells
and may contribute to the mitogenic response of the periosteum in the early
stages of bone repair.
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proliferation and differentiation of osteoprogenitor
cells are modulated by tGF-b, iGF, BMp-6, BMp-2 and BMp-7, and the
vascular ingrowth into the repairing bone is regulated by vEGF and FGF-2.
the temporal response of GF in fracture repair has been investigated in
mice.
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tGF-b and PDGF increase in the first two days from the seeding of
bone marrow cells in osteogenic medium, then decrease but increase again
at day 7, with a second peak at day 14. vEGF peaks at day 4 and returns
