Biomedical Engineering Reference
In-Depth Information
2.
Osteogenic Growth Factors and
Cytokines and Their Role in Bone Repair
Louis C. Gerstenfeld, Cory M. Edgar, Sanjeev Kakar,
Kimberly A. Jacobsen, and Thomas A. Einhorn
2.1 Introduction
transforming growth factor
) super-
family, angiogenic factors, and parathyroid
hormone/parathyroid hormone-related peptide
(PTH/PTHrP). Major emphasis has been
directed to these molecules because their activ-
ities constitute current targets of pharmaco-
logical studies to promote or alter bone healing.
Short reviews of the fi broblast growth factor
(FGF) and Wnt families of factors are also pre-
sented in the context of their known functions
in skeletal development and intended use as
therapeutic agents. The second half of the
review (sections
β
(TGF-
β
Ontogenetic development is initiated at the
time of fertilization and terminates with the
differentiation, growth, and maturation of spe-
cialized tissues and organs. These developmen-
tal processes are characterized by molecular
specialization that accompanies cellular differ-
entiation and tissue morphogenesis. Most
developmental processes terminate after birth
or when animals reach sexual maturity, but
some morphogenetic processes are reinitiated
in response to injury in specifi c tissues. One
such regenerative process is the repair of skel-
etal fractures and bone tissue after surgery,
a process that recapitulates specifi c aspects
of the initial developmental processes in the
course of healing [
) is focused on the
anatomy and cell biology of bone healing, on
what is known about the temporal and spatial
expression of the various cytokines during
bone healing, and how cytokines and morpho-
gens may therapeutically modify the repair
process.
2
.
3
-
5
]. Several aspects of
the postnatal tissue environment of fracture
healing, however, are unique and differ from
what occurs in embryological and postnatal
development. Understanding how cytokines
and morphogens affect fracture or postsurgical
healing is essential to the development of
pharmacological and molecular approaches
intended to enhance bone healing after surgery
or traumatic injury, as well as to promote skel-
etal tissue engineering.
The fi rst half of this review (Section
58
,
209
2.2 Cytokines, Morphogens,
and Growth Factors:
The TNF-
a
Family
2.2.1 The TNF Family of Cytokines
and Their Intracellular Functions
) will
focus on several groups of soluble protein
factors that regulate postnatal bone repair: the
tumor necrosis factor
2
.
2
TNF was fi rst identifi ed in the early
s, and
a large superfamily of related molecules has
since been identifi ed. So far,
1980
α
(TNF-
α
) family, the
18
members with
17
