Biomedical Engineering Reference
In-Depth Information
days 1 to 4, while others are constantly up-regulated. Genes of the first
group are functionally associated with the repair process including iGF-i,
pdGF, fibroblast growth factor receptor (FGFr), fibronectin, matrix
metalloproteinases, glypican, byglican, osteomodulin, osteonectin, tenascin
C, cartilage collagen (type vi and Xi) and bone collagen (type i, v, vi,
and Xii). in contrast, many of the constantly up-regulated genes control
cell growth and survival, and they fall into activity groups with a general
function such as binding, transport and catalytic activity.
on day 4, osteoblast progenitors differentiate and synthesize immature
osteoid. From the molecular point of view, direct ossification is a relatively
quiet stage and the essential molecular activity is the regulation of cell death.
proteomic analysis reveals that proteins, differentially expressed, belong to
a single interacting network associated with cell death, immune response
and cell signalling, and il6 is strongly expressed and plays a pivotal role
in coordinating the three functional groups.
on day 7, a number of molecular events testify the start of endochondral
ossification that is observed histologically later.
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Chondrogenesis represents
the most active molecular event. Several molecular pathways are active,
including pdGF, vascular endothelial growth factor (vEGF) and peroxisome
proliferator-activated receptor alpha (ppar). in the downstream of the
above-mentioned pathways, the proteins related to pi3K/aKt, a cell survival
signalling, are the most significantly expressed.
on day 14, hypertrophic chondrocytes are the dominant cell type. in the
hard callus, BM is evident and osteoclast-like cells remove cartilage and
create a space where osteoblasts are able to form woven bone. proteins
significantly expressed in this phase suggest that at least six pathways are
potentially active; of these, ppar is involved also at the chondrogenesis
stage, while apoptosis and p38/MAPK signalling are uniquely significant
during endochondral ossification. When endochondral ossification comes
to an end (day 28), bone repair enters the remodelling phase. p13K/aKt,
iGF-i, MapK/ErK and integrins are some of the pathways involved.
among the variety of cells and signalling pathways that regulate bone
repair and regeneration, a central role is the ability of MSC to differentiate
into bone forming cells. By using microarray technology, we have studied
the gene expression profile of human MSC cultured
in vitro
and undergoing
osteogenic induction. the analysis was performed at different time points
until MSC were able to form mineral nodules
in vitro.
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We focused on up-
regulated genes with a biological function relevant to osteogenesis, such as
cell communication, morphogenesis and skeletal development, Wnt signaling,
tGFb signalling, angiogenesis, cell cycle and apoptosis. in the early stage
of differentiation, we observed genes involved in cell cycle, while in further
stages the expression of growth factor signalling pathways, bone-related genes
and adhesion molecules gradually increased. Genes typical of angiogenesis
